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 2011:24(2):74-78

Activity of vancomycin, ciprofloxacin, daptomycin, and linezolid against coagulase-negative staphylococci bacteremia   

M. FAJARDO, R. HIDALGO, S. RODRÍGUEZ, F. F. RODRÍGUEZ-VIDIGAL, A. VERA, M. ROBLES       

 

Objective. Multiresistant coagulase-negative staphylococci (CNS) infections are mainly increased in hospitalized patients. We have studied the activity of vancomycin, ciprofloxacin, daptomycin and linezolid in methicillin-resistant CNS strains, isolated from true blood cultures.
Methods. We collected 87 strains of different CNS species from positive blood cultures. Staphylococci were identified by MicroScan Walkaway (Dade Behring, Siemens) and with the Api ID 32 Staph (BioMerieux, France). The susceptibility to oxacillin, vancomycin and ciprofloxacin was performed by automatic microdilution plate as cited above. The susceptibility to daptomycin and linezolid was performed by Etest (AB BioMerieux, Solna, Sweden). Interpretative criteria were done following the CLSI guidelines.
Results. Eighty-seven CNS strains were studied: 55 (63%) were S. epidermidis, 15 (17%) S. haemolyticus, 10 (12%) S. hominis, and 7 (8%) other species. Fifty-three (61%) strains showed loss of susceptibility to vancomycin, MIC = 2 mg/L. Ciprofloxacin resistance, MIC > 2 mg/L, was observed in 56 (64%) strains. Daptomycin resistance was not observed, with a susceptibility range between 0.032-1 mg/L and modal value of 0.25 mg/L. Ten strains (11.5%) resistant to linezolid were observed. Nine patients were in ICU, where the average length of stay was 38 days (range 16-58 days) and one belonged to Hepato-Pancreatic Surgery, where he stayed for 64 days.
Conclusions. Low susceptibility to vancomycin is frecuent in the CNS strains studied in our hospital. Daptomycin shows a high efficacy against CNS, and it could be useful for the treatment of primary bacteremia or catheter associated bacteremia. The massive and continuous use of linezolid has led to the appearance of resistance. 

 
Rev Esp Quimioter 2011:24(2):74-78 [pdf]

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Rev Esp Quimioter 2011:24(4):184-190

Bacteroides mobilizable and conjugative genetic elements: antibiotic resistance among clinical isolates          


C. QUESADA-GÓMEZ              

The conjugation is one of the most important mechanisms of horizontal gene transfer in prokaryotes, leading to genetic variation within a species and the acquisition of new traits, such as antibiotic resistance. Bacteroides is an obligate anaerobe of the colon and a significant opportunistic pathogen. Antibiotic resistance among Bacteroides spp. is rapidly increasing, largely due to the dissemination of DNA transfer factors (plasmids and transposons) harbored by members of this genus. Transfer factors can be divided into two classes, conjugative and mobilizable. Species of the intestinal Bacteroides have yielded different resistance plasmids, all of which have been intensely studied, the plasmids encode high-level MLS resistance conferred by a conserved erm gene. It has been reported an interesting observation associated with the transfer of several of these types of elements, all of which conferred Tcr and displayed greatly increased transfer efficiency following exposure to tetracycline. Many of the conjugative transposons (CTns) in Bacteroides are related to various genetic elements (such as CTnDOT, CTnERL, NBU and others). CTnDOT carries a tetracycline resistance gene, tetQ, and an erythromycin resistance gene, ermF. Resistance to drugs used to treat Bacteroides infections, such as clindamycin, has also been increasing. These conjugal elements have been found in Bacteroides clinical isolates. Thus, horizontal gene transfer could conceivably have played a role in the rising incidence of resistance in this bacterial group. 

 
Rev Esp Quimioter 2011:24(4):184-190 [pdf]

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Rev Esp Quimioter 2012:25(1):42-46

Phenotypes and mechanisms of resistance to macrolides and lincosamides in Streptococcus agalactiae isolates with clinical significance in an eight-year period (2002-2010)                

F. ARTILES, A. CAÑAS, I. ÁLAMO, B. LAFARGA                               

 

Introduction. Streptococcus agalactiae is the most prevalent agent of invasive disease in the newborn (sepsis, pneumonia, and meningitis), as well as an important cause of puerperal fever, urinary tract infection and surgical site infection. The aim of our study was to know the evolution of macrolide and lincosamide resistance in this microorganism.
Methods. Resistance phenotypes were established according to the erythromycin-clindamycin induction test: M (efflux pump) or MLSB (methylase). Genetic mechanisms were detected by PCR for the following genes: ermB, ermA, ermTR, and mefA/E. Molecular typing was based on chromosomal DNA macrorestriction and detection of fragments using pulsed-field gel electrophoresis.
Results. During 8 years, 300 isolates of S. agalactiae were recovered. Seventy-eight (26%) were resistant to macrolides, and seventy (23%) were resistant to lincosamides. Constitutive MLSB was observed in 21% of the isolates (all but one carrying the ermB gene), with a erythromycin MIC90 ≥ 256 mg/L. Inducible MLSB was observed in 2.3% of the isolates (all carrying the ermTR gene), with a MIC90 of 6 mg/L. M phenotype was observed in 2.7% of the isolates (all carrying the mefA/E gene), with a MIC90 of 6 mg/L. Molecular typing revealed the presence of two major clones (A and B) comprising 56.6% of the isolates. Most of the isolates (90.5%) belonging to clon A carried the ermB gene.
Conclusions. Macrolide resistance in our area is similar to that observed in the rest of Spain, but there has been no increase in the incidence rate along the study period. 

 
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Rev Esp Quimioter 2012:25(3):189-193


Evaluation of the variability in the susceptibility of Acinetobacter baumannii to tigecycline in the same medium with two methods of quantitative diffusion different commercial                 

R. TEJERO, M. CAUSSE, M. A. MORENO, F. SOLÍS, F. RODRÍGUEZ-LÓPEZ, M. CASAL                                                                           

 
Introduction: Tigecycline may be a therapeutic alternative for the control of multidrug-resistant Acinetobacter baumannii, although there is no consensus on the cutoffs or susceptibility to the variability of the minimum inhibitory concentration (MIC) according to the culture medium and strips for the antibiogram against this microorganism by quantitative diffusion method. Therefore, the objective was to verify this variability and propose epsilometer test strip that more closely resemble to the standard method.
Material and methods: 38 strains of A. baumannii were selected and evaluated their susceptibility to tigecycline with two different commercial strips (E-TEST and Liofilchem). MICs were compared with those obtained by the standard technique of microdilution broth.
Results: MICs obtained by the Liofilchem strip were more similar to standard method than those obtained by E-TEST strips.
Conclusion: In the two studied strips, higher MICs to those obtained by the standard method were observed leading to false-positive tigecicline resistance in many cases. However, the Liofilchem strip showed the results more closely resemble to the standard method.

 

Rev Esp Quimioter 2012:25(3):189-193 [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.

 
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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 2011:24(2):79-83

Do general practitioners follow the therapeutical recommendations of cystitis in women?. INURA study   

G.RABANAQUE, A. LÓPEZ, J. M. COTS, C. LLOR       

 

Objective: The management of lower urinary tract infections varies from physician to physician. The aim of this study was to assess whether general practitioners follow the evidence-based guidelines for the management of cystitis in women.
Methods: Cross-sectional study carried out from March to July 2009 in which physicians consecutively registered in a template during a 8-week period the first six episodes of cystitis by means attended at the medical consultation. Age, episode of infection, associated morbidity, antibiotic prescription, and type of antibiotic course (short or long regimen) were determined.
Results: Out of 176 physicians invited to participate, 110 included 658 women with lower urinary tract infections with antibiotic treatment being administered in 634 cases. Short courses were given to 385 women (60.7%) and 249 women were given long schedules (39.3%). A total of 343 out of all noncomplicated cystitis were treated with short courses (62.9%) and 75 out of complicated cystitis were treated with long courses (66.4%). First-choice antibiotics were administered as empiric treatment in only 111 women (17.5%).
Conclusions: These results highlight a poor adherence of general practitioners to current recommendations of clinical practice guidelines in cystitis with a low utilization of first-choice antibiotics. 

 
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Rev Esp Quimioter 2011:24(4):191-197

Outpatient use of topical antimicrobials in Spain associated with other drugs (2005-2007)          


P. MORI, D. MARTÍNEZ, J. BENEIT, E. PACHECO, J. GONZÁLEZ              

Introduction: The consumption of antibiotics for systemic use has been well studied. However, data of topical use in our country are an anecdotal reference in the literature.
Objective: To evaluate the outpatient use of topical antimicrobials in Spain associated with other drugs during the period December 2005 and November 2007.
Methods: A descriptive quantitative study was conducted between December 1, 2005 to November 30, 2007. The sample amounted to a total of 112 drugs, representing 131 dosage forms. The data on consumption of drugs were sold by the company Intercontinental Marketing Services (IMS), while demographic data were obtained from the municipal census of 2006 and 2007. The study variables were grouped into three categories: those relating to consumption, those on medications and other variables such as geographic location and time period.
Results: During the study period the outpatient consumption of topical antimicrobials in Spain was 41.755.951 vials (130.637.368 euros) whose composition included associations between antimicrobials or antimicrobials with other drugs. The average monthly consumption amounted to 1.739.831 vials and 5.443.223 euros. The dermal route of administration was the most dispensed and according to the Anatomical, Therapeutic, Chemical classification system (ATC) and the D07CC subgroup was the most used. The association between tobramycin and dexamethasone ophthalmic suspension as 30% was the drug most used in Spain.
Conclusions: The consumption of topical antimicrobials in Spain during the period 2006-2007 increased by 2.36% in the number of vials and 7.28% in economic cost. These antimicrobials were more used in summer. The average cost of a topical antimicrobial was half (3.13 euros) compared to the average cost of a drug (7.89 euros).group. 

 
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Rev Esp Quimioter 2012:25(1):47-55


Effect of protein binding on the activity of voriconazole alone or combined with anidulafungin against Aspergillus spp. using a time-kill methodology                

F. CAFINI, D. SEVILLANO, L. ALOU, F. GÓMEZ-AGUADO, M. T. CORCUERA, N. GONZÁLEZ, J. GUINEA, J. PRIETO                                                         

 

Objectives: the aims of the study were to explore the activity of total and free (according to protein binding) maximal concentrations achieved in serum after multiple doses of voriconazole 400/200 mg and anidulafungin 200/100 mg against Aspergillus fumigatus and Aspergillus flavus and the human albumin or serum effects on antifungal activity.
Material and methods: Time-kill curves were performed with two A. fumigatus and two A. flavus strains at voriconazole and anidulafungin Cmax concentrations using different media: a) RPMI broth (Cmax-RPMI); b) RPMI with human serum (Cmax-HS), and c) RPMI with human albumin (Cmax-HAlb). In parallel, free-drug (fCmax) concentrations considering theoretical protein binding were performed in RPMI broth. Aspergillus metabolic activity was measured by the XTT reduction assay.
Results: Voriconazol or voriconazole plus anidulafungin reduced >88.4% the metabolic activity of Aspergillus sp. at Cmax-RPMI and fCmax after 48 h of exposition. Anidulafungin alone showed poor metabolic reductions (<80.1% at Cmax-RPMI and <15% at fCmax). Anidulafungin activity, but not voriconazole activity alone or combined decreased in presence of HS or HAlb (more pronounced in A. flavus strains and HAlb). However, anidulafungin Cmax-HS or Cmax-HAlb against A. fumigatus strains were significantly more active (p<0.05) than fCmax in RPMI. These species and culture medium-dependent impact of human protein binding in the activity of anidulafungin was related to macroscopic and microscopic differences among mycelial mat grown in RPMI, HS or HAlb in whose XTT retention was different.
Conclusions: Synergism could not be demonstrated due to the high activity showed by voriconazole. Protein binding has not impact on voriconazole activity and this impact is considerably less than predicted by free concentration extrapolated from theoretical binding rate on anidulafungin. The XTT colorimetric assay needs to be standardized for use with Aspergillus spp. since without DMSO extraction the activity of echinocandins in a free-human protein RPMI medium could be overestimated. 

 
Rev Esp Quimioter 2012:25(1):47-55 [pdf]

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