Rev Esp Quimioter 2010:23(4):169-176

Antifungal agents in the treatment of systemic infections: Relevance of mechanism of action, activity profile and resistances 

M. CUENCA-ESTRELLA   

 

The availability of different therapeutic alternatives has modified the treatment of systemic fungal infections. There commendations of antifungal therapy vary according to species which causes the mycosis and its susceptibility. Consequently, the knowledge of action mechanism, activity profile and resistances to antifungal agents are essential for the clinical practice. Amphotericin B is the antifungal agent exhibiting the broadest spectrum of activity, it is a fungicidal drug and resistances have been hardly ever described. The triazoles compounds also have a broad spectrum, but their massive use for some therapeutic indications has led to emergence of strains and species of yeasts with resistance to fluconazole and of filamentous fungi itraconazole resistant.The echinocandins exhibit fungicidal effects for yeasts andafungistatic activity against moulds, and secondary resistance to these agents is uncommon.   

 
Rev Esp Quimioter 2010:23(4):169-176 [pdf]

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Rev Esp Quimioter 2011:24(2):84-90

Resistance of Streptococcus pneumoniae isolated from Lebanese patients between 2005 and 2009    

Z. DAOUD, M. KOURANI, R. SAAB, M. A. NADER, M. HAJJAR        

 

Introduction: Streptococcus pneumoniae is an important organism in view of its prevalence and ability to cause serious infections; its resistance to antimicrobial agents is increasing worldwide. The purpose of this study was to evaluate the patterns of resistance of S. pneumoniae to penicillin, macrolides and various other antibiotics in strains isolated from Lebanese patients.
Methods: 121 strains isolated between January 2005 and January 2009 from two university hospitals in Beirut were identified and tested for MIC determination using the E-test method. The presence of erm(B) and mef(A/E) genes was investigated using PCR.
Results: The majority of the strains (73.5%) were isolated from respiratory tract infections, 50.4% were isolated in winter, 15.7% were invasive strains, 61.9% came from male patients, and 68.5% from adults. Out of 121 isolates, 58 were susceptible to penicillin, 61 were intermediate, and 2 were fully resistant to this antibiotic. Amoxicillin-clavunanic acid and cefpodoxime showed 100% activity on all tested isolates. In general, the MICs90 appear to fluctuate within the same range over the four years. The erm(B) gene was detected in 85.3% of the isolates, mef(A/E) in 19.5% whereas erm(A) was not detected in any of the macrolide resistant strains.

Discussion: The results of this study have important impact on the empirical antibiotic prescriptions; the increasing prevalence of resistance jeopardises the treatment choices posing a serious threat. Further surveillance and epidemiological serotyping are needed to monitor the local and regional resistance patterns and to track the spread route of resistance.  

 
Rev Esp Quimioter 2011:24(2):84-90 [pdf]

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Rev Esp Quimioter 2011:24(4):198-203

Treatment of chronic hepatitis C virus infection. A study of best predictors for response          


N. OSPINA, J. L. RODRÍGUEZ, M. HERNÁNDEZ, C. GARCÍA, J. M. MARTÍN, E. REDONDO, L. OLIVIA, M. J. PENA              

Objective: The aim of this study was evaluate the rate of sustained viral response (SVR) and the influence of different factors on the SVR in patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon alfa 2a and ribavirin.
Methods: We retrospectively analysed 272 naïve patients with chronic hepatitis C who had been treated for 24 weeks or 48 weeks and had been followed for an additional 6 months thereafter.
Results: Out of 272 patients, 243 completed the entire treatment. The overall SVR rate in intent-to-treat analysis was 66.5% and in treated patients was 74.5%. In an univariate analysis, the SVR was associated with age <40 years (84.4%), pre-treatment viral load <500.000 IU/ml (86.9%), non-1 genotype HCV (86.4%), non cirrhosis or pre-cirrhosis (76.5%), rapid virologic response (RVR) (91.4%) and early virologic response (EVR) (83.8%). In the multivariate logistic regression analysis, the presence of an infection caused by a non-1 genotype and to achieve ERV were independent predictors of SVR. The RVR and histological stage of liver disease were not included in the multivariate analysis because these data were not available in most of the patients. The PPV and NVP of RVR were 91.5% and 48.7% respectively, of EVR were 83.8% and 95.8% respectively and of complete EVR were 91.3% and 78.7%, respectively.
Conclusions: The SVR was higher than in other studies. The genotype and EVR were independent factors to predict the effect of antiviral therapy. The EVR had a high NPV and the complete EVR a high PPV. 

 
Rev Esp Quimioter 2011:24(4):198-203 [pdf]

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Rev Esp Quimioter 2012:25(1):56-64


Clinical characteristics and outcome of patients with pandemic 2009 Influenza A(H1N1)v virus infection admitted to hospitals with different levels of health-care 
                

M. GUTIÉRREZ-CUADRA, J.L. GONZÁLEZ-FERNÁNDEZ, P. RODRÍGUEZ-CUNDIN, C. FARIÑAS-ÁLVAREZ, M. V. SAN JUAN, J. A. PARRA, M. CARRASCOSA, M. C. FARIÑAS                                                         

Background. The outcome of patients with influenza A 2009 (H1N1)v virus infection taking into account hospital type has not been elucidated.
Objectives. To compare risk factors, clinical features and outcome of patients admitted to 3 public hospitals with different levels of health-care.
Methods: Prospective study of all non-pregnant adult patients admitted to 3 hospitals with pandemic H1N1 infection, from June 1 to December 31 and followed up until 1 month after discharge.
Results. During the study period, 111 patients with a mean age of 49 years (15-89) were hospitalized: 52 in hospital 1 (900-bed tertiary-teaching-hospital), 33 in hospital 2 (315-beds secondary-hospital) and 26 in hospital 3 (150-beds primary-care-hospital).Overall 80% of patients had at least 1 comorbid condition with no differences between hospitals. Symptoms or signs on admission were similar except for cough (P=0.01) more frequent in patients in hospital 1 and dyspnea (P=0.05), myalgia, arthralgia (P=0.04) and hypoxemia (P=0.009) present in more patients in hospital 2. In-hospital mortality rates were not statistically different between hospitals. In the stepwise analysis, independent predictors of mortality were pneumonia on admission (adjusted OR=8.68, 95%CI 1.0-82.43) and cardiac complications during hospitalization (adjusted OR=13.2, 95%CI 1.67-103.98).
Conclusions. Mortality of patients with pandemic H1N1 infection was influenced by patients underlying conditions, severity of disease (pneumonia) on admission and complications during hospitalization. Hospital-characteristics do not appear to have influenced severe outcome.. 

 
Rev Esp Quimioter 2012:25(1):56-64 [pdf]

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Rev Esp Quimioter 2012:25(3):199-205


Coagulase-negative Staphylococcus bacteraemia: prognosis factors and influence of antibiotic treatment                   

A. FERNÁNDEZ-RUFETE, E. GARCÍA-VÁZQUEZ, A. HERNÁNDEZ-TORRES, M. CANTERAS, J. RUIZ, J. GÓMEZ                                                                          

 
Introduction: Coagulase-negative staphylococci (CNS) are the most frequent isolated microorganism in blood cultures; mortality has been associated to severity and to adequacy of empirical treatment but the relevance of the latter is not clearly recognised. The aims of the study were to analyze clinical and microbiological factors related to mortality in patients with CNS bacteraemia and the influence of empirical treatment in prognosis.
Patients and methods: a prospective cohort study of patients with CNS bacteraemia was performed (January to June 2010) at a university-affiliated hospital; a determination of clinical significance was made and true bacteraemia was defined according to CDC criteria. We analysed epidemiological, clinical and microbiological variables related to mortality.
Results: a total of 269 cases were included (97 were considered true bacteraemia); 92% survived and mortality was 8% (1.6% CNS bacteraemia related mortality). Staphylococcus epidermidis was the most frequent isolated species; 93 patients were included in the related mortality study of patients with true bacteraemia. Factors associated to mortality in the bivariate analysis (p<0.05) were: Winton score I-III, presence of pacemakers, sepsis or infective endocarditis and persistent bacteraemia. Adequate empirical treatment was not associated to survival.
Conclusions: severity at onset, the development of septic complications and having a pacemaker are associated to mortality in patients with CNS bacteraemia; in our cohort, inadequate empirical treatment is not related to mortality.

 

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Rev Esp Quimioter 2010:23(2):63-71

Differences in the use of tigecycline between ICU patients and non-ICU patients

F. ALVÁREZ-LERMA, L. BLANCO, J.A. RODRÍGUEZ, S. GRAU, D. CONDE-ESTÉVEZ, S. LUQUE

 

Background. Tigecycline is a new broad spectrum antibiotic that is predominantly used for the treatment of severe infections both in critically ill patients admitted to the ICU and in non-ICU patients with less severe clinical conditions.
Objetive. To assess differences in the use of tigecycline between ICU patients and non-ICU patients treated with this antibiotics.
Materials and methods. Retrospective, cohort, observational study in which cases were defined as patients who received one or more doses of tigecycline over the first 18 months after approval of the drug in a general hospital. Clinical characteristics, indications, route of administration, clinical response, tolerability and outcome were recorded in the groups of ICU and non-ICU patients. Descriptive data and results of the comparison of both cohorts are presented.
Results. A total of 103 were included in the study, 34 (33%) of which received tigecycline during their stay in the ICU. ICU patients compared to non-ICU patients had a higher SAPS II score on admission (39.0 ± 11.8 vs 26.3 ± 8.0, p < 0.001) and at the time of starting tigecycline treatment (42.2 ± 12.6 vs 25.6 ± 8.2, p < 0.001), were treated with antibiotics for more days (21.4 ± 30.6 vs 13.6 ± 30.5 days, p < 0.012) and received a greater number of antibiotic agents concomitantly (85.3% vs 47.8%,p < 0.001), presented a higher selection of emerging bacterial flora (41.2% vs 15.9%, p = 0.005), particularly Pseudomonas aeruginosa (20.6% vs 2.9%, p = 0.006), higher rate of clinical failure (58.8% vs 21.7%, p < 0.001), longer hospitalization (51.2 ± 39.4 vs 28.7 ± 26.3 days, p < 0.001) and higher overall mortality rate (50% vs 14.5%, p < 0.001) and infection-attributed mortality (20.6% vs 7.2%, p = 0.047).
Conclusions. The patient that receives tigecycline in the ICU has a higher severity level and worse clinical outcome than the non-ICU patient treated with this antibiotic. It is necessary to optimize the indications of tigecycline in the ICU to improve the clinical results.

 
Rev Esp Quimioter 2010:23(2):63-71 [pdf]

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Rev Esp Quimioter 2010:23(4):177-183

Prophylaxis and treatment of invasive fungal infection in neutropenic patients 

C. VALLEJO, M. ROVIRA   

 

Prophylaxis and treatment constitute the basis for reducing the mortality due to IFI. Prophylaxis is currently the standard practice in most hospitals and is recommended by the principal guidelines. Fluconazole has proved to be useful to prevent and reduce the mortality due to yeast IFI in several contexts. Although its use has led to the emergence of some resistant strains of Candida, it has not been a generalized problem and the number of lives saved has been worth it. But its major disadvantage is the lack of impact on IFI by molds. So, in patients at high risk for IFI due to filamentous fungi, it is necessary the employ of extended spectrum drugs. For the empirical and preemptive approach, it is necessary to have in mind which fungi have to be covered and  the spectrum of the available antifungal agents. For the treatment of established infection by Candida spp., before the identification of species, we must consider different host (like the use or not of prophylactic fluconazole) and clinical factors (like the evidence or not of diseminated infection or severe sepsis). Primary combination of antifungal agents for the treatment of invasive aspergillosis has to be considered in cases of central nervous system disease, respiratory failure, serious sepsis,  and extensive or cavitated pulmonary lesions.    

 
Rev Esp Quimioter 2010:23(4):177-183 [pdf]

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Rev Esp Quimioter 2011:24(2):91-95

Antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus strains from outpatient individuals    

L. GARCÍA-AGUDO, M. HUERTAS, M. A. ASENCIO EGEA, R. CARRANZA, P. GARCÍA-MARTOS         

 

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged worldwide as a cause of infections among patients without risk factors. This CA-MRSA is different from nosocomial strains in terms of epidemiology, microbiology and clinical manifestations. We report the epidemiologic characteristics and resistance to antimicrobial agents of CA-MRSA strains isolated in the last three years in the Microbiology Lab of Hospital General La Mancha-Centro (Alcázar de San Juan, Ciudad Real).
Methods: We performed a retrospective analysis of microbiological cultures in patients with S. aureus diagnosed from 2007 to 2009 in La Mancha-Centro Health-Care Area, within Castilla-La Mancha Community.
Results: The distribution of CA-MRSA in the studied period was 26 out of a total of 97 S. aureus isolates in 2007 (26.8%), 40/113 in 2008 (35.4%) and 57/157 in 2009 (36.3%). The percentage from purulent skin and soft tissue infections was 63.4%. All strains were susceptible to linezolid, quinupristin/dalfopristin, and glycopeptides. The resistance was high to fluoroquinolones (94.3%), erythromycin (87.0%), tobramycin (82.9%), and clindamycin (65.3%).
Conclusions: CA-MRSA isolates percentage increased along the period of the study. The majority were obtained from skin and soft tissue specimens. The most commonly associated antimicrobial resistance was to fluoroquinolones, erythromycin, tobramycin and clindamycin. An understanding of the CAMRSA epidemiology is important to prevent these organisms from becoming endemic in the world. 

 
Rev Esp Quimioter 2011:24(2):91-95 [pdf]

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Rev Esp Quimioter 2011:24(4):204-208

Predictive factors for pneumonia in adults infected with the new pandemic A (H1H1) influenza virus          


E. LERMA, L. SORLÍ, M. MONTERO, V. MAS, E. LÓPEZ, C. VILAPLANA, F. ÁLAVAREZ-LERMA, H. KNOBEL, J. P. HORCAJADA              

Background: On April 2009 a new A (H1N1) influenza virus was identified with a higher incidence of severe outcome in younger people, most of them with pneumonia.The objective of our study was to identify the predictive risk factors of pneumonia in patients with the new A (H1N1) influenza virus infection.
Methods: Prospective cohort study of adults infected with the new A (H1N1) influenza virus, admitted in a universitary hospital, from june 2009 to January 2010. Pneumonia was defined as the presence of any pulmonary infiltrate of any distribution with no other evident cause, in the chest radiography. A comparative analysis was made with patients with A (H1N1) influenza without pneumonia.
Results: 281 patients with influenza A (H1N1) were treated. Thirty of them (10.6%) had pneumonia and 11 (3.9%) required intensive care. The global mortality was 0.7%. For the comparative analysis, 42 patients with influenza A (H1N1) without pneumonia were analysed (20 hospitalized and 22 nonhospitalised).
In the multivariate analysis, obesity (BMI>30), (OR: 3.8; IC 95%: 0.99-15.0), time since symptom onset until hospital admission (OR 1.34; IC 95% 1.04-1.72), serum C reactive protein levels (OR:1.10; IC 95%: 0.98-1.24) and serum IgG2 levels (OR:1.08; IC 95%: 1.0- 1.01), were identified as independent risk factors for pneumonia.
Conclusion: Obesity, delay in medical care and higher levels of C reactive protein and IgG2 were predictive factors for pneumonia in adult patients with A (H1N1) influenza infection. 

 
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Rev Esp Quimioter 2012:25(1):65-73


Analysis of treatments used in infections caused by Gram-positive multiresistant cocci in critically ill patients admitted to the ICU 
                

F. ÁLVAREZ-LERMA, M. PALOMAR, P. OLAECHEA, J. INSAUSTI, M. J. LÓPEZ, M. P. GRACIA, R. GIMENO, I. SEIJAS                                                          

The appearance of new antimicrobials with activity against Gram-positive multiresistant cocci and knowledge of the limitations of glycopeptides has represented an important change in the use of these antibiotics.
Objetive. To analyze at the national level changes in the use of antibiotics with specific activity against Gram-positive multiresistant cocci in critically ill patients admitted to the ICU as well as the characteristics of patients treated with these agents and the forms of administration.
Material and methods. Retrospective cohort study of patients admitted to the ICU for more than 24 hours between 2008 and 2010 in the ENVIN-HELICS national registry. Cases were defined as patients who had received one or more of the following antibiotics: vancomycin, teicoplanin, linezolid or daptomycin. The characteristics of patients who used one or more of these agents were compared with those treated with other antibiotics. Indications and forms of use of each antibiotic were assessed. Descriptive results are presented.
Results. A total of 45,757 patients, 27,982 (61.2%) of whom received 63,823 antimicrobials were included in the study. In 6,368 (13.9%) patients, one or more antibiotics specifically active against Gram-positive multiresistant cocci were given. There was a predominance of the use of vancomycin and linezolid and an important increase in the prescription of daptomycin (+320%) and linezolid (+22.4%). In more than 95% of cases, linezolid and daptomycin were prescribed for the treatment of infections, whereas vancomycin and teicoplanin were used for prophylaxis in 20-25% of cases. Between 75% and 80% of indications for treating infections, antibiotics were used empirically except for daptomycin which was used as a directed treatment in 43% of the cases. Only in one third of the indications for empirical treatment, susceptible microorganisms were identified (appropriate treatment).
Conclusions. The use of antibiotics with activity against Gram-positive multiresistant cocci remained stable around 14% of all indications. The use of vancomycin and linezolid predominated and there was a clear trend towards an increase in the use of daptomycin and linezolid and a decrease in the use of glycopeptides. Empirical treatments were considered appropriate in only one third of cases.
  

 
Rev Esp Quimioter 2012:25(1):65-73 [pdf]

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