Rev Esp Quimioter 2013:26(4):298-311

Prevention and control of nosocomial and health-care facilities associated infections caused by species of Candida and other yeasts

JAVIER PEMÁN, RAFAEL ZARAGOZA, MIGUEL SALAVERT             

Knowledge of the epidemiology of invasive fungal diseases caused by yeasts (Candida spp., especially) in health care settings allows the establishment of the levels necessary for its prevention. A first step is to identify groups of patients at high risk of nosocomial invasive fungal infections, establish accurate risk factors, observing the periods of greatest risk, and analyze the epidemiological profile in genera and species as well as the patterns of antifungal resistance. Secondly, mechanisms to avoid persistent exposure to potential fungal pathogens must be programed, protecting areas and recommending measures such as the control of the quality of the air and water, inside and outside the hospital, and other products or substances able to cause outbreaks. Finally, apart from the correct implementation of these measures, in selected patients at very high risk, the use of antifungal prophylaxis should be considered following the guidelines published.

Rev Esp Quimioter 2013:26(4):298-311 [pdf]

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Rev Esp Quimioter 2013:26(4):312-331

Bugs, hosts and ICU environment: Countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting 

EMILIO MASEDA, JOSÉ MENSA, JUAN-CARLOS VALÍA, JOSE-IGNACIO GOMEZ-HERRERAS, FERNANDO RAMASCO, ENRIC SAMSO, MIGUEL-ANGEL CHIVELI, JORGE PEREIRA, RAFAEL GONZÁLEZ, GERARDO AGUILAR, GONZALO TAMAYO, NAZARIO OJEDA, JESÚS RICO, MARÍA JOSÉ GIMENEZ, LORENZO AGUILAR             

ICUs are areas where resistance problems are the largest, and they constitutes a major problem for the intensivist’s clinical practice. Main resistance phenotypes among nosocomial microbiota are: i) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and ii) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallobetalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has lead to multidrug resistance, a worrisome problem nowadays. This article reviews by microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors.

Rev Esp Quimioter 2013:26(4):312-331 [pdf]

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Rev Esp Quimioter 2013:26(4):332-336

Antimicrobial resistance in tuberculosis 

JUAN BAUTISTA GUTIÉRREZ-AROCA, PILAR RUIZ, MANUEL CASAL             

Although drug resistance in tuberculosis is by no means a new problem, multiple drug resistance is a cause of increasing concern. This study investigated first-line drug resistance in Mycobacterium tuberculosis strains isolated in a hospital environment and strains submitted as the Reference Center from 2000 to 2010. A total of 650 cultures were tested against first-line using the BACTEC MGIT 960 system. Resistance to first-line drugs was detected in 142 strains, (21.85%). A total of 2% were multiresistant (MDR). Of the strains resistant to first-line drugs, the greatest resistance was found to isoniazid (7.38 %) followed by rifampin and streptomycin (3.85%), pyracinamide (2%), and ethambutol 1.23%. Only one strain was resistant to four drugs. Values. In view of the resistance observed, careful surveillance of drug resistance is recommended.

Rev Esp Quimioter 2013:26(4):332-336 [pdf]

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Rev Esp Quimioter 2013:26(4):337-345

Staphylococcus aureus infections and factors associated with resistance to methicillin in a hospital emergency department 

JUAN GONZÁLEZ-CASTILLO, CATERINA CENCI, ESTHER RODRIGUEZ-ADRADA, FRANCISCO JAVIER CANDEL, FERNANDO DE LA TORRE-MISIEGO, CRISTINA FERNÁNDEZ, FRANCISCO JAVIER MARTÍN-SÁNCHEZ             

Objective. Assessment of the characteristics of patients with Staphylococcus aureus (SA) infections, and factors associated with resistance to methicillin in a hospital emergency department (ED) in Spain.
Materials and Methods. All adult patients admitted between January 2007 and December 2010 with a SA infection confirmed by a positive culture in a sample obtained in the hospital emergency department were selected for enrolment. Epidemiological, clinical, therapeutic and microbiological variables were retrospectively collected from the patients’ medical charts. The variable assessed within the primary outcome of the study was the isolation of methicillin resistant Staphylococcus aureus (MRSA). For the purpose of the analysis, the sample was divided in terms of the presence or not of the resistance to methicillin and a logistic regression analysis was performed to identify the factors associated with isolation and empirical antibiotic coverage of MRSA.
Results. A total of 207 patients with a confirmed SA infection were included in the study analysis, with a mean age of 64.7 (SD 20) years. MRSA was isolated in a total of 63 (30.4%) patients, and a linear incremental trend was observed over the course of the study (p=0,047). MRSA was empirically covered in the emergency department on an average rate of one in three patients. Independent factors associated with the isolation of MRSA were: age above 65 years [OR 2.97 (95% CI 1.24 to 7.1), P = 0.014], severe baseline functional dependence [OR 2.41 (95 % 1.02 to 5.69), P = 0.045], chronic obstructive pulmonary disease [OR 4.83 (95% CI 1.88 to 12.42), P = 0.001], history of antibiotic treatment within the previous 2 months [OR 4.94 (95% CI 2.27 to 10.76), P <0.001] and a confirmed urinary infection [OR 5.98 (95% CI 1.65 to 21.69) p = 0.007]. Independent factors associated with empiric coverage of MRSA in the ED were history of antibiotic treatment within the previous 2 months [OR 3.88 (95% CI 1.76 to 8.57), P <0.001] and the presence of a catheter device [OR 6.28 (95% CI 1.64 to 24.07), P = 0.007].
Conclusions. Resistance to methicillin appears to be increasingly frequent in patients infected with SA admitted in our emergency department and there appears to be a need for a more optimal empiric antibiotic treatment in these patients.

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Rev Esp Quimioter 2013:26(4):346-352

Influence of ethnicity on the pharmacokinetics of amikacin 

MELISA BARRANTES-GONZÁLEZ, SANTIAGO GRAU, DAVID CONDE-ESTÉVEZ, ESTHER SALAS, MÓNICA MARÍN-CASINO             

Objective. Despite the increasing ethnic diversity, there are few studies of its influence on the pharmacokinetics of amikacin. The objective of this study was to compare the pharmacokinetics of amikacin in different populations: Asian, Hispanic, North Africans and Caucasian.
Methods. A retrospective observational study was performed in a tertiary teaching hospital during eight years. It was included all patients with intravenous amikacin treatment in extended interval dosing regimen with therapeutic drug monitoring of amikacin. Pharmacokinetic parameters were analysed. A bivariate and multiple linear regression statistical analysis were carried out.
Results. 164 patients were included: 7 asians, 135 Caucasians, 11 Hispanics and 11 from North Africa. It was shown a lower plasma concentrations of amikacin in North Africa population due to its greater clearance.
Conclusions. Amikacin plasma concentrations monitoring is advisable in patients from North Africa in order to avoid subtherapeutic concentrations.

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Rev Esp Quimioter 2013:26(4):353-359

Prosthetic joint infections due to methicillin-resistant and methicillin-susceptible staphylococci treated with open debridement and retention of the prosthesis 

EDUARD TORNERO, LAURA MORATA, JUAN C MARTÍNEZ-PASTOR,  GUILLEM BORI, JOSEP MENSA, ALEX SORIANO             

Objectives. To compare the specific characteristics, the outcome and the predictors of failure of prosthetic joint infections (PJI) due to methicillin-resistant (MRS) and methicillin-susceptible staphylococci (MSS) treated with open debridement and retention of the implant.
Material and methods. PJI due to MRS or MRS prospectively registered in a database from 1999 to 2009 were retrospectively reviewed.
Results. During the study period, 96 patients met the inclusion criteria of the study. The mean follow-up period was 3.9 years and at least 2 years in all patients. The failure rate was 25%. The only variable significantly associated with failure in the global cohort was polymicrobial infection (59.3% vs. 40.7%, p=0.036). Thirty-four (35.4%) patients had an infection due to MRS and 62 (63.6%) due to MSS. Among MSS infections, 95.2% corresponded to primary arthroplasties while 29.4% of PJI due to MRS were after revision arthroplasties (p=0.001). CRP was significantly higher in PJI due to MSS (5.2 mg/dl vs 9.1 mg/dL, p=0.02).The failure rate (20% vs 27%, p=0.62) was very similar in MSS and MRS groups.
Conclusion. PJI due to MRS were mainly coagulase-negative staphylococci, more frequent after revision arthroplasties, had a lower inflammatory response, and had a similar failure rate than MSS infections.

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Rev Esp Quimioter 2013:26(4):360-368

Effectiveness of liposomal amphotericin B in patients admitted to the ICU on renal replacement therapy 

FRANCISCO ÁLVAREZ-LERMA, MONTSERRAT RODRIGUEZ, MARI CRUZ SORIANO, MERCEDES CATALÁN, ANA MARÍA LLORENTE, NIEVES VIDART, MARÍA GARITACELAYA, ENRIQUE MARAVI, ELISABETH FERNÁNDEZ REY, FRANCISCO ALVARADO, MARTA LÓPEZ-SÁNCHEZ, BERNABÉ ALVAREZ-SÁNCHEZ, DAVID GRANADO, ELISABETH QUINTANA AND THE STUDY GROUP OF LIPOSOMAL AMPHOTERICIN B IN THE ICU             

Introduction. This study was designed to compare the effectiveness of liposomal amphotericin B (L-AmB) in ICU patients with and without renal replacement therapy (RRT).
Methods. Observational, retrospective, comparative and multicenter study conducted in critically ill patients treated with L-AmB for 3 or more days, divided into two cohorts depending on the use of RRT before or within the first 48 hours after starting L-AmB. Clinical and microbiological response at the end of treatment was evaluated.
Results. A total of 158 patients met the inclusion criteria, 36 (22.8%) of which required RRT during the ICU stay. Patients with RRT as compared with those without RRT showed a higher APACHE II score on admission (21.4 vs 18.4, P = 0.041), greater systemic response against infection (P = 0.047) and higher need of supportive techniques (P = 0.002). In both groups, main reasons for the use of L-AmB were broad spectrum and hemodynamic instability. A higher daily dose of L-AmB was used in the RRT group (4.30 vs 3.84 mg/kg, P = 0.030) without differences in the total cumulative dose or treatment duration. There were no differences in the clinical response (61.1% vs 56.6%, P = 0.953) or microbiological eradication rate (74.1% vs 64.6%, P = 0.382). In patients with proven invasive fungal infection, satisfactory clinical response was obtained in 74.1% and microbiological eradication 85.7%.
Conclusions. Although the study sample is small, this study shows that L-AmB is effective in critically ill patients admitted to the ICU requiring RRT.

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Rev Esp Quimioter 2013:26(4):378-386

Treatment of invasive fungal infections in high-risk haematological patients: What have we learnt in the past 10 years? 

CARLOS VALLEJO, LOURDES VÁZQUEZ, JOSÉ RAFAEL CABRERA MARTÍN, ENRIC CARRERAS, JULIO GARCÍA RODRÍGUEZ, ISABEL RUIZ CAMPS, JESÚS FORTÚN, JOSEP MENSA, JOSÉ BARBERÁN             

Invasive fungal infection (IFI) caused by filamentous fungi remains a very severe infectious complication in patients with onco-haematological diseases. Last advances in the diagnostic and therapeutic fields, today we know that their contributions are limited. Something similar can be said of clinical trials especially in relation to some changes in the characteristics of the host. The development of promising diagnostic techniques and the relative expansion in the number of antifungal agents has been associated with diversification of therapeutic strategies (prophylaxis with extended-spectrum azoles and preemptive antifungal treatment). However, the low sensitivity of AGA testing in some circumstances, and the potential delay in starting treatment due to logistic reasons, has been reflected by a greater mortality in certain type of patients and a significant increase in the days of treatment. All these circumstances has once again focus attention to the empirical approach as a central strategy in high-risk patients. The objective of this article is to review the clinical experience in the treatment of IFI in onco-haematological patients according to data published in the literature in the last decade and to present a set of recommendations.

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Rev Esp Quimioter 2014:27(1):1-16

Clinical indications for therapeutic drug monitoring of antifungal agents. In the way for optimizing the treatment of fungal infection                                 
 

EMILIO CENDEJAS-BUENO, MANUEL CUENCA-ESTRELLA, ALICIA GÓMEZ-LÓPEZ               

Therapeutic drug monitoring as a tool in the management of infectious diseases has been introduced in therapy with anti-infective agents for years. Nowadays, it has taken importance in the management of fungal diseases due to the appearance of new antifungal drugs such as new-generation azoles. These azoles have pharmacokinetic characteristics that hinder a proper use to ensure efficacy and minimize toxicity. Monitoring of serum concentrations may help in the better use of these anti-infective agents, as well as in a better management of drug interactions, infectious disease and adverse effects. It has resulted in saving costs of treatment and in avoiding inadequate dosages. This review will attempt to clarify the role of the antifungal agents Therapeutic Drug Monitoring, highlighting the role of azole compounds.

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Rev Esp Quimioter 2014:27(1):17-21

Antifungal susceptibility of clinical isolates of Scopulariopsis species                                
 

VALLE ODERO, LIDIA GARCÍA-AGUDO, INMACULADA GUERRERO, PILAR AZNAR, PEDRO GARCÍA-MARTOS, MANUEL RODRÍGUEZ-IGLESIAS               

Introduction. Scopulariopsis is a common soil saprophyte. In the last years the infections caused by Scopulariopsis species have increased, included superficial and invasive mycoses. This fungi has been reported resistant in vitro to some antifungal agents, although there is little information about this. The aim of the study was to establish in vitro antifungal susceptibility of clinical isolates of Scopulariopsis species against to broad-spectrum antifungal agents.
Methods. A total of 28 Scopulariopsis strains (10 S. brevicaulis, 7 S. koningii, 3 S. acremonium, 3 S. candida, 3 S. flava, 1 S. brumptii and 1 S. fusca) were tested using Sensititre YeastOne and broth microdilution methods to determine the minimum inhibitory concentrations (MICs) to amphotericin B, fluconazole, itraconazole, posaconazole, voriconazole and 5-fluorocytosine, and minimun effective concentration (MECs) to anidulafungin, caspofungin and micafungin.
Results. Our data confirm the high in vitro resistance of Scopulariopsis to antifungal agents. Anidulafungin, caspofungin, micafungin (MICs ≥8 mg/L), 5-fluorocytosine (MICs ≥64 mg/L), and fluconazole (MICs ≥128 mg/L) were inactive in vitro in all species. MICs of amphotericin B (range 2 to ≥8 mg/L) and itraconazole (0.5 to ≥16 mg/L) were high. The best antifungal activity was observed for posaconazole and voriconazole (0.5 to ≥8 mg/L). With Sensititre YeastOne method MICs obtained slightly lower. Scopulariopsis candida, S. flava and S. fusca were the most resistant species, while S. acremonium and S. brevicaulis showed the lowest MICs.
Conclusions. MICs of all tested antifungal agents for Scopulariopsis were very high. Infections caused by Scopulariopsis species may not respond to antifungal treatment. Voriconazole is the drug of choice for treatment. We consider it appropriate to add amphotericin B in serious infections.

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