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Rev Esp Quimioter 2018; 31(1): 35-42

Interferon-free treatments in patients with hepatitis C genotype 3 infection in a tertiary hospital

JUAN CARLOS DEL RIO-VALENCIA, ROCÍO ASENSI-DIEZ, RAQUEL MADERA-PAJIN, LUCÍA YUNQUERA-ROMERO, ISABEL MUÑOZ-CASTILLO

Introduction. Hepatitis C virus genotype 3 represents a unique entity within HCV treatment and multiple studies have documented that HCV genotype 3 infection is associated with more rapid disease progression than other genotypes, resulting in increased risk of cirrhosis, hepatocellular carcinoma, and all-cause mortality. In the current study, we further evaluated the real-world effectiveness of 12 weeks of ledipasvir/sofosbuvir ± ribavirin (LDV/SOF ± RBV) and sofosbuvir + daclatasvir (SOF + DCV) for treatment-naive or treatment-experienced patients infected with HCV genotype 3, with or without cirrhosis.
Material and methods. Retrospective and observational study carried out in a third level hospital. Study period: April 2015 to January 2016. Inclusion criteria: Patients with HCV genotype-3 infection treated either with LDV/SOF ± RBV or with SOF + DCV during study period treated for 12 weeks. The patients that were treated during 24 weeks were excluded and those treated with peg-interferon. The main endpoint measured was the sustained virologic response (SVR) at 12 weeks (SVR12) and the secondary endpoint was SVR at 24 weeks (SVR24).
Results. During the study period, 603 patients were treated in our hospital: 71 with genotype 3. We included 46 patients who were treated with LDV/SOF ± RBV or SOF + DCV for 12 weeks. A 43.75% (7/16) of all patients treated with LDV/SOF achieved SVR12, 90% (9/10) of the patients treated with LDV/SOF+RBV achieved SVR12 and 95% (19/20) of the patients treated with SOF+DCV achieved SVR12. There was statistically significant difference (p=0.001) between LDV/SOF respect to SOF+DCV and between LDV/SOF with regard to LDV/SOF +RBV (p=0.018) used to treat HCV genotype 3 infection.
Conclusions.  In conclusion, in our cohort of patients, the combination of SOF + DCV followed by LDV/SOF + RBV 12 weeks were the most effective in patients with HCV genotype 3 and with cirrhosis (SVR12 90% and 80%, respectively) and in those without cirrhosis (SVR12 100% in both combinations). All patients who achieved SVR12 also achieved SVR24, regardless of the regimen received.

Rev Esp Quimioter 2017; 31(1): 35-42 [Full-text PDF]

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Rev Esp Quimioter 2008;21(Núm. Ext. 1):26-34

Pharmacoeconomics of infection in the intensive care unit

S. Grau ,  F. Álvarez-Lerma 

  

The intensive care unit (ICU) services are areas that have a need for greater use of economic resources, including the frequent use of higher priced drugs, standing out among them those corresponding to antimicrobial agents. This situation has led many hospital sites to include the ICU within those units needing special monitoring in regards to the use of drugs and the introduction of cost-containment programs in the ICU. It is possible that indiscriminate restriction in the financial cost section aimed at antimicrobial agents may mean that these drugs may be prescribed more inappropriately, a practice that has been related with greater mortality of patients with severe infections. Thus, the pharmacoeconomics of infection in the ICU should be analyzed through the study of different aspects and not only from the strict analysis of direct cost of the antimicrobial agents. In the present review, the cost of infection in the ICU has been analyzed, contemplating a series of perspectives that are considered essential and demonstrating, at all times, that evaluation of the cost of acquiring the antimicrobial agent as the only element for its choice should be avoided. The analysis was made by evaluating cost of infection in the ICU, the strategies for the control of use and cost of antibiotics in the ICU, importance of adequate early empiric treatment, the costs associated with the development of bacterial resistances and pharmacoeconomic studies.

 

Key words: Pharmacoeconomics. ICU. Infection. Pharmacoeconomic studies. Antibiotic policy. Early antibiotic treatment.

Rev Esp Quimioter 2008;21(Núm. Ext. 1):26-34  [pdf]   

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Rev Esp Quimioter 2008;21(Núm. Ext. 1):14-25

Up-date on the treatment of serious fungal infections

M. Borges Sá 

  

Introduction. In recent years, there has been an exponential increase in the incidence of severe fungal infections with elevated morbidity-mortality. An attempt is currently being made to obtain faster and more reliable diagnostic tests for a certainty diagnosis and to be able to use clinical criteria to identify patients who could be candidates to receive early antifungal treatment and thus be able to improve the prognosis.

Sources. For the purposes of this article, we reviewed the indexed literature for the last 15 years. We used different key words: invasive fungal infection (IFI), invasive aspergillosis, candidemia, and candidiasis, emerging fungi, prophylaxis and antifungal treatment (empiric, directed and pre-emptive treatment).

Development. The approach to antifungal treatment is also undergoing significant changes. These go from the appearance of new molecules, new generations of other already known ones and also changes in the more «traditional» approach in its use. This article is structured on the use slope of antifungal agents in non-neutropenic critical patients from their prophylaxis, empiric treatment, aimed towards new strategies (pre-emptive treatment or early therapy or combined use of antifungal agents). Furthermore, an attempt is being made to obtain simple scores to indicate their early onset in patients with high risk of IFI.

Conclusions. The combination of rapid identification of patients with risk (scores), faster diagnostic methods and finally more effective antifungal treatment with the providing of new antifungal agents and/or strategies will be essential to try to decrease the elevated morbidity-mortality in severe patients.

  

Key words:Invasive fungal infections. Candidemia. Invasive aspergilosis. Antifungal therapy. Pre-emptive treatment.

Rev Esp Quimioter 2008;21(Núm. Ext. 1):14-25  [pdf] 

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Rev Esp Quimioter 2008;21(Núm. Ext. 1):9-13

New therapeutic options for the treatment of multiresistant bacteria in the ICU

F. Barcenilla Gaite ,  A. Jover Sáenz ,  M. Vallverdú Vidal ,  D. Castellana Perelló 

  

The number of new antimicrobial drugs in the health care clinical practice has decreased gradually and significantly in the last 15 years. At the same time, there has been an increase in the appearance of microorganisms with resistance to conventional antibiotics, above all in intensive care units (ICU). Within this group, Methicillin-resistant Staphylococcus aureus (MSRA) and methicillin-resistant coagulase- negative staphylococci, vancomycin-resistant enterococci, Pseudomonas aeruginosa and Acinetobacter baumanii resistant to carbapenemics and extended-spectrum ß-lactamase-producing (ESBL) Enterobacteria are the most important. These pathogens are frequently also resistant to other groups of antibiotics such as aminoglycosides, fluoroquinolones and macrolides. New recently introduced antimicrobial agents are available to combat these resistances. These are active mainly against gram positive bacteria resistant strains and in a more timely way against gram negative ones or both. Among the first group, the following stand out: daptomycin (a lipopeptide bactericide for parenteral use) and linezolid (oxazolidinone with bacteriostatic activity for parenteral and oral use). On its part, ertapenem (a carbapenem parenteral bactericide) and tigecyclin (a parenteral bacteriostatic tetracycline) are active against ESBL enterobacteria, the latter also being active against non-fermented gram positives and gram negatives, except for P. aeruginosa. Possibly, the introduction of these new compounds and other futures ones pending introduction will not only improve antimicrobial diversification but also serve to limit the spreading of these microorganisms.

 

Key words: Multiresistant microorganisms. Daptomycin. Linezolid. Ertapenem. Tigecyclin. Therapeutic strategy.

Rev Esp Quimioter 2008;21(Núm. Ext. 1):9-13 [pdf] 

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Rev Esp Quimioter 2008;21(Núm. Ext. 1):7-8

 Epidemiological aspects of mycosis in the critical patient

J. Pemán García 

  

Fungemia, generally causes by Candida spp., is the most frequent deep mycoses in the critical patient and is many times clinically undistinguishable from bacterial septicemia. Less frequently, respiratory or disseminated mycosis produced by Aspergillus or other filamentous fungi, such as Scedosporium, Fusarium, Pneumocystis, Acremonium or zygomycetes have been described. Currently, invasive candidiasis is the fourth cause of nosocomial infection in Europe and the USA. Furthermore, in the SCOPE study, Candida is the third microorganism isolated from the blood culture in the ICU and the mortality that can be attributed to it reaches 25 %-38 %. Currently, the incidence of candidemia has been estimated to be 2 cases per every 1,000 admissions in the mixed critical units and 9.9 cases in the critical surgical units. On its part, invasive aspergillosis is observed in 1.25 % of the patients admitted to the ICU and mostly affects patients with chronic bronchopathy treated with glucocorticoids. It is considered as an indicator of bad prognosis and is associated to very high mortality rates (40%-100 %).

 

Key words:  UCI. Candidemia. Fungemia. Aspergillosis.

Rev Esp Quimioter 2008;21(Núm. Ext. 1):7-8 [pdf] 

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Rev Esp Quimioter 2008;21(Núm. Ext. 1):2-6

Problematic bacteria

J. L. Muñoz Bellido 

  

Introduction. Because of the special characteristics of the critical patients, infections are one of the primary complications they suffer so that multiresistant microorganisms take on a special importance in this type of patient.

Sources. Search in Medline using the words ICU (Intensive Care Unit), multidrug resistant, critical patient.

Development. Glycopeptide resistant enterococci show a reduced prevalence in our setting and the VISA and hVISA are isolated sporadically. MRSA is, on the other hand, a major problem. In 2003-2005, it was already accounting for 28%-38% of the S. aureus isolated in the ICU, with a high percentage of fluoroquinolone (>90%) and macrolide (>65%) co-resistance. The extended-spectrum beta-lactamase producing enterobacteria (BLEE) also are a growing problem, worsened by their frequent co-resistance with fluoroquinolones, about 30% according to some studies. Carbapenem resistance in A. baumannii has doubled in recent years, with values greater than 50%, almost always associated to enzymes of the OXA group. P. aeruginosa also maintains high resistance values (25%-30% of resistance to imipenem, ceftazidime or ciprofloxacin), but more stable. However, high rates of multi-resistance are also observed, now about 50% of the isolations of imipenem resistant P. aeruginosa are also to fluoroquinolones. As a whole, recent studies show that the multiresistance has multiplied in recently years by 5 in P. aeruginosa and by 7 in A. baumannii. Conclusions. Multiresistant bacteria infections are one of the greatest problems to combat in critical patients and control of their spreading and the development of active antimicrobials against them is one of the principal challenges at present.

  

Key words: Critical patients. Intensive Care Unit (ICU). Multi-resistant bacteria. Nosocomial infection. Resistance 

 

Rev Esp Quimioter 2008;21(Núm. Ext. 1):2-6 [pdf]  

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Rev Esp Quimioter 2008;21(4):234-258

Guidelines for the treatment on infections caused by methicillin-resistant Staphylococcus aureus

J. Mensa ,  J. Barberán ,  P. Llinares ,  J.J. Picazo ,  E. Bouza ,  F. Álvarez-Lerma ,  M. Borges Sá ,  R. Serrano ,  C. León ,  Xavier Guirao Garriga ,  J Arias ,  E Carreras ,  M Sanz ,  J. Á. García Rodríguez 

  

Infections due to methicillin-resistant Staphylococcus aureus (MRSA) have undergone important changes in the last five years that have influenced the choice of therapy: i) increase of their frequency in hospital-associated settings and, more recently, in community settings; ii) better knowledge of clinical implications of the pharmacokinetic and pharmacodynamic properties of vancomycin; iii) improvement of current standard methods for rapid detection of MRSA in clinical samples; iv) clear evidence that vancomycin is losing efficacy against MRSA with MIC > 1 μg/mL; and v) appearance of new antibiotics suitable for use in these infections (linezolid, daptomycin, tigecyclin). Under this situation guidelines for the treatment of common infections caused by MRSA appear to be necessary to improve the efficacy and reduce the mortality.

 

Key words: Methicillin-resistant S. aureus (MRSA). MRSA guidelines. New antibiotics.

Rev Esp Quimioter 2008;21(4):234-258 [pdf] 

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Rev Esp Quimioter 2008;21(4):224-233

Hepatotoxicity by antibiotics: update in 2008

M. Roble ,  R. J. Andrade 

  

Although antibiotics are the most commonly incriminated drugs in instances of hepatotoxicity in medical literature. However, it is mainly due to its wide prescription and the absolute risk of hepatotoxicity related to antibiotic use is thought to be low. Nevertheless, among the different penicillins, amoxicillin-clavulanate is the single leading drug involved in hepatotoxicity in cohorts of patients with druginduced liver injury (DILI), representing between 12.8% to 14% of the cases. It is the most frequent cause of hospitalization for DILI. The incidence of amoxicillin-clavulanate induced hepatotoxicity has been estimated to be 9.91 per 100 000 users and its clinical presentation varies, the type of injury strongly influenced by age, with the hepatocelullar pattern predominating in younger patients and the cholestatic/mixed ones in older subjects. Among macrolides, erythromycin is a classical example of drug capable of inducing cholestatic injury. Recently, concern has arisen regarding telithromycin, a new generation macrolide, is hepatotoxic came from the identification of several cases of DILI related to this drug, with a typical signature, including abrupt commence of fever, abdominal pain, jaundice and ascites in some cases. Tetracyclines, especially in intravenous high doses, may be associated with dose-dependent microvesicular steatosis, and minocycline has been involved in an autoimmune like type I hepatitis. Quinolones, in spite of their extensive use in patients with cirrhosis and biliary infections, have been very rarely associated with hepatotoxicity.

 

Keywords: Hepatotoxicity. Antibiotics. Amoxicillin-clavulanate. Age.

 

Rev Esp Quimioter 2008;21(4):224-233 [pdf]

 

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Rev Esp Quimioter 2008;21(4):217-223

Staphylococcus aureus bacteremia in Castellón General Hospital (2001-2005)

S. Sabater Vidal ,  R. Moreno Muñoz 

  

Objective. The aim of this study was to know the frequency of bacteremias produced by Staphylococcus aureus and the sensibility that strains showed, as well as the clinical characteristics of the patients.

Method. We retrospectively studied cases of S. aureus bacteremia detected in our hospital from 2001 to 2005 and also reviewed medical histories from patients during 2005.

Results. A total of 295 cases of S. aureus bacteremia were detected in this study. Annual distributions of the cases were as follows: 35, 54, 62, 64 and 80. By gender, 62.7 % related to males and 37.3 % to females. A total of 58.6 % of the patients were admitted to medical services and 49 % were older than 65 years. Regarding resistance, 34 % of the strains showed resistance to oxacillin, 33 % to ciprofloxacin, 41 % to erythromycin and 4.4 % to gentamicin. In one-third of the patients, S. aureus was isolated in other samples, the catheter being the most common. A total of the 73.5 % of the patients had some baseline disease and the most frequent predisposing factor was the intravascular catheter. The bacteremias were nosocomial-acquired in 73.5 % of the cases.

Conclusions. In our hospital, S. aureus bacteremia and oxacillin resistance has been increasing over the years of this study.    

 

Key words: Staphylococcus aureus. Bacteremia. Oxacillin resistance. Catheter. Nosocomial.   

 

Rev Esp Quimioter 2008;21(4):217-223 [pdf]

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Rev Esp Quimioter 2008;21(4):213-216

Evaluation of the cefoxitin 30 μg disk diffusion method for detection of methicillin-resistance in selected Staphylococcus aureus isolates

N. Batista Díaz ,  I. Gutiérrez González ,  M. Lara Pérez ,  F. Laich ,  S. Méndez Álvarez 

  

Oxacillin tests may fail to detect some methicillinresistant S. aureus populations. The objective of this study is to evaluate the discriminative capacity of the Clinical and Laboratory Standards Institute (CLSI) disk diffusion method with a cefoxitin 30 μg disk on S. aureus isolates with unusual phenotypic characteristics of antimicrobial resistance. We studied 53 clinical S. aureus isolates. The antimicrobial susceptibility of all isolates was routinely studied by the VITEK 2 System (bioMérieux). Methicillin resistance was also studied by CLSI oxacillin method and confirmed by a previously described multiplex polymerase chain reaction (PCR) method which permits S. aureus identification and simultaneous detection of methicillin resistance. MecA positive isolates presenting a diffuse growth within the zone of inhibition when exposed to oxacillin were considered heteroresistant; mecA negative, oxacillin intermediate or resistant isolates were considered borderline. All the isolates were tested with a cefoxitin 30 μg disk, according to the CLSI guidelines (susceptibility: > 22 mm; resistance: < 21 mm). Control strains for all assays included MRSA ATCC 43300 and MSSA ATCC 25923. The isolates formed four groups. Group I: 20 multiresistant, oxacillin susceptible and mecA negative isolates; group II: 16 resistant or with intermediate oxacillin susceptibility and mecA negative isolates; group III: 11 heteroresistant and mecA positive isolates; group IV: six mecA positive isolates with atypical resistance profiles (penicillin and oxacillin, or ciprofloxacin and erythromycin resistance). Thirty-five mecA negative isolates included in groups I and II showed inhibition zones > 22 mm; one isolate from group II showed 20 mm. The 17 mecA positive isolates from groups III and IV showed resistance to cefoxitin disk. The 30 μg cefoxitin disk diffusion method is proposed as an efficient method for the detection of methicillin resistance and permits a clear determination set S. aureus isolates, even those with atypical antimicrobial characteristics.

  

Key words: Staphylococcus aureus. Cefoxitin. Methicillin-resistance

 

Rev Esp Quimioter 2008;21(4):213-216 [pdf]

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