Rev Esp Quimioter 2010:23(4):158-168

Nosocomial candidemia: new challenges of an emergent problem 

J. GÓMEZ, E. GARCÍA-VAZQUEZ, A. HERNÁNDEZ, C. ESPINOSA, J. RUIZ GÓMEZ   

 

Candida spp. are currently one of the most common causes of bloodstream infections in hospitals. Over the last two decades there has been a shift towards a greater involvement of non-Candida albicans as the cause of candidemia. Several of these non-albicans spp. (e.g., C. glabrata and C.krusei) exhibit resistance to traditional triazole antifungals (fluconazole), and cross-resistance with newer triazoles (voriconazole), focusing attention on the first-line use of antifungals such as the echinocandins, which possess improved activity against fluconazole-resistant strains. Early and adequate empirical treatment as well as early removing of the central catheters are the main factors related to mortality; thus it is necessary to implement guidelines of empirical treatment (including these aspects) in patients with risk factors and possible candidemia. Recent treatment guidelines from the Infectious Diseases Society of America (IDSA) recommend an echinocandin as primary therapy for non neutropenic or neutropenic patients with moderately severe to severe candidiasis and for patients at risk for infection with a triazole-resistant strain; the increasing MIC of echinocandins in case of C. parapsilosisis also an emerging concern. Clinicians should remain vigilant to prescribe early empiric treatment of patients at risk of having candidemia.   

 
Rev Esp Quimioter 2010:23(4):158-168 [pdf]

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Rev Esp Quimioter 2010:23(1):43-47

Evaluation of pharmacodynamic target attainment with vancomycin treatment of bacteremia due to Staphylococcus aureus methicillin resistant

J. A. LEPE, M. V. GIL-NAVARRO, M. D. SANTOS-RUBIO, J. BAUTISTA, J. AZNAR

 

Objective: The objective of the study is to evaluate the ability of standard vancomycin dosing strategies actually recommended to attain the pharmacodynamic target of an area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC24h) to minimum inhibitory concentration (MIC) ratio greater than 400:1 for patients with a suspected or documented methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia by individual analysis and Monte Carlo simulation.
Material and methods: The study included all patients admitted with suspected or proven MRSA infection during the years 2007-2008, and who were initially treated with vancomycin at a dose of 30 mg/kg/day, and underwent pharmacokinetic monitoring. The area under the curve of vancomycin serum concentration versus time from 0 to 24 hours (AUC24h) was calculated as daily dose/clearance total (D24h/CL). Additionally, we studied 45 isolates of MRSA obtained from blood cultures in the period 2007-2008. The MIC to vancomycin was determined using Epsilon-test®. The PK-PD parameter calculated was AUC24h/MIC. Microsoft
Excel was used to perform a 10.000 subject Monte Carlo simulation. An AUC24h/MIC ≥ 400 was assumed as the target attainment.
Results: In the individual study, the percentage of patients with AUC24h/MIC50/90 ≥ 400 was 50%. The probability (%) of attaining AUC24h/MIC ratio values ≥ 400 by Monte Carlo simulation was of 66%. The vancomycin MIC value from which the scenario would have to wait a suboptimal treatment (target <90%) was >1 mg/L.
Discussion: This study shows that in the population studied to achieve a vancomycin AUC24h/MIC ≥ 400 is not always attained with the standard dose. Therefore, one would expect a high probability of suboptimal vancomycin AUC24h/MIC ratios for patients infected with organisms with vancomycin MICs of >1 mg/L treated with doses of 30 mg/kg/day.

 
Rev Esp Quimioter 2010:23(1):43-47 [pdf]

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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 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.

 
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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 2010:23(2):53-62

The microbiologist and the catheter related infection

J. GARCÍA-RODRÍGUEZ, M. DE PABLOS, A. GUTIÉRREZ

 

Different multicentre epidemiological studies such as ENVIN-HELICS or EPINE, have remarked that catheter related bloodstream infection (CRBI) is an increasingly condition in hospital environment. The microbiologist plays a major role in the diagnosis, either by recommending what type of catheter must be considered for confirmatory diagnosis, when these samples must be sent for culture, when is indicated to perform surveillance studies of the catheter and what results are clinically significant to be informed. In this paper, differentaspects of the CRBI, such as the pathogenesis, etiology, epidemiology and diagnosis are reviewed. The different microbiological diagnostic methods, both conservatives and those involving the removal of the catheter are up-to-dated.

 
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Rev Esp Quimioter 2010:23(4):184-189

Experience of micafungin in patients requiring extrarenal depuration 

F. ALVAREZ-LERMA, S. GRAU, Y. DÍAZ, J. FERNÁNDEZ   

 

Introduction. The use of extrarenal depuration techniques is increasingly frequent in patients admitted to the ICU. The use of these procedures has been related to a decrease in plasma concentrations of several antimicrobials, among which fluconazole. The activity of antifungal agents depends on achievement on adequate concentrations in plasma and at the site of infection. Micafungin is a new antifungal drug recently introduced in our country.
Objective. To review the published experience of pharmacokinetic (PK) parameters of micafungin in patients requiring some type of extrarenal depuration procedures during their stay in the ICU.
Results. Three studies with data on PK parameters of micafungin during the use of this drug in continuous venovenous hemodialysis (2 publications) and continuous hemodiafiltration (1 publication) were retrieved. In all of them, minimal variations in the plasma concentration of micafungin at the entry and exit sites of the hemofilter and a negligible or minimal presence of micafungin in the ultrafiltration fluid were demonstrated.
Conclusions. Adjustment of the doses or the interval between doses of micafungin during the use of extrarenal depuration techniques in critically ill patients admitted to the ICU is not necessary.   

 
Rev Esp Quimioter 2010:23(4):184-189 [pdf]

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Rev Esp Quimioter 2010:23(2):72-75

Cefditoren versus ceftazidime in inducer-substrate combinations for the evaluation of AmpC production in a disc approximation test

F. CAFINI, L. AGUILAR, L. ALOU, M. J. GIMÉNEZ, D. SEVILLANO, M. TORRICO, N. GONZÁLEZ, P. CORONEL, J. PRIETO 

 

Objective: To evaluate cefditoren in inducer-substrate combinations to screen for AmpC induction.
Methods: 100 clinical isolates (25 P. aeruginosa, 25 E. cloacae, 14 M. morganii, 13 S. marcescens, 12 C. freundii, 7 P. rettgeri, and 4 E. aerogenes) were tested by the Kirby-Bauer disc approximation method using cefditoren and ceftazidime discs as substrates, and cefditoren and imipenem discs as inducers.
Results: None of the strains showed induction of AmpC with cefditoren-ceftazidime as inducer-substrate combination. Imipenem-cefditoren as inducer-substrate combination was not useful for evaluating strains of P. aeruginosa since no inhibition zones surrounding the cefditoren disc were found. Among evaluable enterobacteria (those showing substrate inhibition zone), inducible Amp C was detected in 48 out of 63 (76.2%) with cefditoren, and in 33 out of 68 (48.5%) isolates with ceftazidime as substrate. Significantly (p= 0.013) higher number of AmpC producers were detected with cefditoren versus ceftazidime (76.2% vs. 48.5%), due to the differences found for E. cloacae (72.8% vs. 21.7%; p= 0.0009) and S. marcescens (100% vs. 54.5%; p= 0.03). Higher mean reductions of diameters around substrate discs were found for cefditoren (4.17 mm) vs. ceftazidime (3.79 mm), reaching statistical significance (p<0.05) for indol-positive proteae: M. morganii (5.32 mm vs. 3.92 mm) and P. rettgeri (3.47 mm vs. 2.64 mm).
Conclusion: Cefditoren showed no induction capability, and when used as substrate (with imipenem as inducer) it offered detection rates of AmpC inducible enterobacteria higher than the imipenem-ceftazidime combination, mainly for Enterobacter spp. and Serratia spp., with higher diameter reductions for indol-positive proteae.

 
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Rev Esp Quimioter 2010:23(4):190-195

Significance of lower respiratory tract cultures yielding  Aspergillus spp. growth in a hospital without  transplant patients   

P. LUCENA, J. BARBERÁN, G. EROLES, J. J. GRANIZO, M. J. GIMÉNEZ, N. MIR, L. AGUILAR, J. PRIETO   

 

Introduction: Isolation of Aspergillus spp. in non-neutropenic, non-transplant patients with chronic obstructive pulmonary disease (COPD) usually treated with corticosteroids is not easily interpretable. A retrospective review of clinical records corresponding to cultures (respiratory samples) yielding Aspergillusspp. in non- transplant patients was carried out.

Methods: Patients were assigned to four categories: colonization, possible, probable or definitive aspergillosis. A logistic regression model (step–wise procedure) was performed using as dependent variable mortality, and as independent variables those showing differences (p≤0.1) in the bivariant analysis.

Results:Sixty-nine patients were identified. Most were elderly (68.1% ≥65 years), male (73.9%), presented comorbidities(84.1% Charlson index ≥3), COPD (76.8%), were receiving high corticosteroid doses (66.7%), and had previously received antibiotics (94.2%). Forty-five cases were colonizations, 4 possible, 15 probable and 5 definitive aspergillosis. A. fumigatus was isolated in 75.4% patients:  66.7% colonized, 75% possible,93.3% probable and 100% definitive aspergillosis. Colonized patients were older (71.9 ± 11.9 vs. 65.1 ± 9.2 years; p= 0.018) and presented higher (p=0.034) comorbidity index than patients with aspergillosis. Mortality was 31.1% in colonized vs. 62.5% in aspergillosis (p=0.012).

Conclusion: The isolation of A. fumigatus was associated with an increased probability of aspergillosis, with statistical association in the multivariate analysis between mortality and variables related to chemotherapy (no antifungal treatment), disease (diagnostic category) and immunity (leukocytosis).    

 
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Rev Esp Quimioter 2010:23(2):76-80

Variability in the sensitivity to tigecycline against Acinetobacter baumannii in different culture medium

A. TENORIO-ABREU, J. M. EIROS, E. RODRÍGUEZ-MOLINS, D. ANDALUZ, F. BOBILLO, M. DOMÍNGUEZ-GIL, R. ORTIZ DE LEJARAZU 

 

Introduction. The tigecycline may represent a therapeutic alternative for the control of multiresistant A. baumannii, although there is no consensus regarding the cutoff points for sensitivity or variability of MIC as a function of culture medium used for the antibiogram against this microorganism. Therefore, our objective was to verify this variability, and propose the culture medium that comes closest to the standard method.
Methods. We selected 41 strains of carbapenem-resistant A. baumannii. We analyzed the sensitivity to tigecycline in different culture medium: Mueller Hinton agar Oxoid commercial (C-MH), Mueller Hinton fresh agar BD and Co., USA (F-MH) and ISO-sensitest fresh agar Oxoid, using the E-test and disk. The MICs were compared against those obtained using the technique standard of macrodilution.
Results. The mean MIC and inhibition diameters obtained in the different culture medium corresponded to 9.26 mg/L and 15.1 mm in diameter for MH-C, 1.71 mg/L and 22.7 mm for MH-F; 2.68 mg/L and 20.8 mm for ISO-sensitest. Half the MIC obtained by the standard method of dilution was 0.47 mg/L (SD = 0.21), with values between 0.25 and 1 mg/L.
Conclusion. In the three growth media studied, MICs superior to the standard are observed, which is false to interpret resistance in many cases. However, the medium that comes closer more that of reference is the MH-F.

 
Rev Esp Quimioter 2010:23(2):76-80 [pdf]

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