Factors associated with daptomycin consumption in French hospitals between 2019 and 2020: A nationwide surveillance study.

OBJECTIVES: This study aimed to investigate factors associated with daptomycin consumption in French healthcare facilities (HCF) between 2019 and 2020. METHODS: Antibiotic consumption expressed as number of defined daily doses (DDD) per 1,000 patient-days (PD) and antimicrobial resistance (AMR) expressed as incidence densities per 1,000PD were extracted each year from the nationwide surveillance network run by the SPARES project (Surveillance and Prevention of Antimicrobial RESistance in hospitals), collecting data at ward level among voluntary HCFs using standardized methodology and webtool. All HCF participating both in 2019 and 2020 were included. A multivariable linear regression was fitted. RESULTS: Among 622 HCFs, we analyzed daptomycin consumption and AMR data in 1,637 clinical wards. Incidence densities of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) were the highest in intensive care unit wards (0.54 and 6.83 respectively in 2020). On the most adjusted model, the year 2020 was correlated with a higher daptomycin consumption (1.53; p = 0.01). A greater number of inpatient beds (0.01; p < 0.001), the presence of orthopedic surgery activity in the HCF (1.66; p < 0.02), MRSA (4.38; p < 0.001) and MRCNS (0.61; p < 0.001) incidence densities were associated with a higher daptomycin use. The final model explained 18% of the observed variance. CONCLUSIONS: This study showed that daptomycin consumption was correlated to MRSA and MRCNS incidence densities, to the year 2020 and to non-modifiable HCF-related factors. Prevention of coagulase-negative staphylococci infections should be considered by antimicrobial stewardship teams when daptomycin use is going up in HCF.

Patterns of antibiotic use in hospital-acquired infections.

BACKGROUND: Monitoring the use of antimicrobials in hospitalized patients is critical owing to the risk of resistance selection. This study aimed to describe the patterns of antimicrobial prescription for the most frequent healthcare-associated infections (HAIs) in France, relating drugs and microbiological data. METHODS: We used data from the 2017 point-prevalence survey of HAI and antimicrobial use in France, a large nationally representative sample survey of inpatients. We sought unambiguous correspondence between individual indications of antibiotic regimen and HAI sites to determine which molecules were directed towards which pathogen, considering its resistance profile. RESULTS: Among 75,698 adult patients from 401 hospitals, 5.1% had an active HAI and 4.3% were being treated for an HAI. The two most frequent antibiotic indications were lower respiratory tract (LRTI, 27.7%) and urinary tract infections (UTI, 18.4%). For LRTI, the most prescribed antibiotic was amoxicillin-clavulanic acid (27.6%) and most frequently isolated pathogens (each accounting for around 17% of isolates) were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Meticillin-resistant S. aureus LRTI was more likely to be treated with linezolid. For UTI, ofloxacin, ceftriaxone, amoxicillin/co-amoxiclav were most-prescribed (∼13% each) and E. coli predominantly isolated (52.0%). Extended-spectrum beta-lactamase-producing E. coli UTI were more likely treated by fosfomycin, pivmecillinam or ertapenem. CONCLUSIONS: This study provides a baseline of antimicrobial use in relation to microbiological information in patients with the most common HAIs. These results can serve to direct future efforts in antimicrobial stewardship. Our work could be extended to a broader population, notably in Europe where similar surveys have been conducted.

Antibiotic misuse: How to evaluate the costs?

OBJECTIVE: Few studies have assessed the costs associated with the misuse of antibiotics in hospitals in France, despite the value of health economic data to inform antibiotic stewardship activities. We aimed to identify the methodological tools used to assess the cost of antibiotic misuse in hospitals. METHODS: We performed a literature review using the major electronic medical databases. An index of relevance was developed to assess the intrinsic quality of selected articles. RESULTS: Four hundred and three articles were retrieved, but 35 were selected for analysis. Most studies investigated the inadequate choice of the antibiotic molecule (n=17), the incorrect treatment duration (n=9), and the administration of an inappropriate dosage (n=7). Only three studies were medical/economic evaluations of specific interventions, such as prescription control by pharmacists or the implementation of a new diagnostic test. Considering our aim, the relevance of the studies was limited: few had defined the economic assessment as the primary objective or had detailed the method for calculating costs. Nevertheless, the misuse evaluation was usually better described. CONCLUSIONS: Despite these limits, key factors for measuring antibiotic misuse (i.e., molecule choice, dosage) in relation to the costs (i.e., over/under prescription, hospital stay, staff remuneration) might serve as the basis for the development of a reference methodology to value the costs of misuse. The application of this methodology on identified situations of antibiotic misuse would help hospital decision-makers to justify resource allocation for implementing antimicrobial stewardship activities.

Antibiotics associated with acquisition of carbapenem-resistant Pseudomonas aeruginosa in ICUs: a multicentre nested case-case-control study.

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains are involved in severe infections, mostly in ICUs. Exposure to antibiotics other than carbapenems may be associated with isolation of CRPA; therefore, we aimed to identify those antibiotics using the case-case-control study design. Methods: A case-case-control study was conducted in 2015 in a prospective multicentre cohort that included 1808 adults hospitalized in 2009 in 10 French ICUs. Patients were screened for P. aeruginosa at admission to the ICU and then weekly. Cases were patients with CRPA and patients with carbapenem-susceptible P. aeruginosa (CSPA) isolation. Controls were patients without P. aeruginosa isolation, matched with each case according to centre, length of stay and hospitalization period. Effects of antibiotic exposure were explored, after adjusting for prior treatment with carbapenems and confounding factors comprising colonization pressure with two logistic regression models. The two models were compared to identify specific risk factors for CRPA isolation. Results: Fifty-nine CRPA, 83 CSPA and 142 controls were compared. In adjusted multivariable analyses, exposure to carbapenems and to antibiotics belonging to the group of ß-lactams inactive against P. aeruginosa were independent risk factors for CRPA isolation (OR, 1.205; 95% CI, 1.079-1.346 and OR, 1.101; 95% CI, 1.010-1.201, respectively). Conversely, exposure to ß-lactams active against P. aeruginosa was an independent protective factor for CSPA isolation (OR, 0.868; 95% CI, 0.772-0.976). Conclusions: Besides carbapenem exposure, exposure to ß-lactams inactive against P. aeruginosa was a specific risk factor for CRPA isolation. Clinicians should counterweigh the potential benefits of administering these antibiotics against the increased risk of CRPA infection.

[Cooperation according to French Law "hospital, patients, health and territories": Pharmacists' involvement in Aquitaine region]. / Missions de coopération introduites par la loi « hôpital, patients, santé et territoires ¼ : participation des pharmaciens d'officine en Aquitaine.

BACKGROUND: In 2009, the French Act "Hospital, Patients, Health and Territories" (loi "Hôpital, Patients, Santé et Territoires") reorganized the outpatient care pathway and defined missions aimed at improving cooperation between pharmaceutical and medical professionals. Five years later, we conducted a survey among community pharmacists in order to assess the appropriation of these missions and the way cooperation was implemented. We also aimed to investigate factors that could hamper or ease the development of these activities in order to identify actions needed to improve pharmacists' involvement. METHODS: In partnership with the local health authorities "Agence régionale de santé", we conducted a survey via an online questionnaire sent to pharmacy holders in July 2014 in Aquitaine region. Information was collected about the pharmacies, involvement in collaborative activities, and barriers to cooperation. RESULTS: Overall, 20% (249) of pharmacists responded to the survey. They owned predominantly rural pharmacies (46%) or neighborhood pharmacies (41%), with two pharmacists per pharmacy (48%). Regarding collaborative activities, the majority of pharmacists (78%) had conducted interviews with their patients taking vitamin K antagonist therapy and they were willing to continue (87%). The implication was less common concerning other actions such as referent pharmacist for nursing homes (19%) or activities relating to therapeutic educational programs for patients with chronic conditions (34%). The vast majority of respondents (85%) were not aware of opportunities to become a correspondent pharmacist. The main obstacles for engaging in these activities were the lack of time, lack of knowledge about these missions and the lack of remuneration. We identified differences in pharmacists' involvement in collaborative activities depending on selected characteristics of the pharmacies. CONCLUSION: The findings of this survey underlined pharmacists' acceptance of these missions and suggest that better information and appropriate remuneration could enhance commitment. Recent changes in the legal framework (establishment of "pharmaceutical fees", extension of the scope of pharmaceutical interviews) enable funding for collaborative practices between medical practitioners and pharmacists, thus encouraging better coordination in the patient care pathway.

Factors associated with the prevalence of antibiotic use for the treatment of hospital-acquired infections at 393 French hospitals: a regional variation analysis.

OBJECTIVE: The present study investigated regional variations in antibiotic use for the treatment of hospital-acquired infections (HAIs) in France by means of a multilevel analysis, to identify targets for quality improvement. METHODS: Data were obtained from the 2001 and 2006 French national point-prevalence surveys of HAIs and antibiotic use. The present study was conducted using data from 393 nonteaching public hospitals. Data included patient characteristics calculated at the hospital level (mean age and proportion of patients with the following: HAI, presence of a vascular catheter, presence of a urinary catheter, surgical procedure, and immunodeficiency) and hospital characteristics (size and presence of an intensive care unit). The regional effect was measured using a random intercept on a regional variable. RESULTS: Overall, the prevalence of antibiotic use was 5.35% for both study years. The most commonly used antibiotics for HAIs were fluoroquinolones (2001, 1.33%; 2006, 1.35%) and combinations of penicillins with a ß-lactamase inhibitor (2001, 0.92%; 2006, 1.02%). Mapping of antibiotic use showed wide variation between regions. The regional effect explained 3% of antibiotic variation in the unadjusted analysis. In the multivariable analysis, hospital size, high prevalence of patients with immunodeficiency, and infection characteristics explained 45% of the variability in antibiotic use. The regional effect was not retained in the final model. CONCLUSION: The pattern of antibiotic use for HAIs differed over time, and regional variations were mostly explained by patient characteristics; there was no regional effect. Models that take data hierarchy into account are essential to better approach antibiotic use and develop relevant strategies for improvement.

[Antimicrobial consumption reported through standardized reports on infection control activities, relationship with the ICATB public reporting indicator]. / Consommation des antibiotiques rapportée via les bilans standardisés de lutte contre les infections nosocomiales et relation avec l'ICATB.

OBJECTIVE: The study's objective was to describe the evolution of antibiotic consumption between 2006 and 2008 in French health care facilities (HCF) its relations with the national policy of good antibiotics use using the ICATB score. METHOD: Data from standardized reports on infection control activities collected from 2006 to 2008 by the Ministry of Health (antibiotic consumptions and elements of antibiotic stewardship of every HCF) were analyzed with linear regression models to multilevel random intercept adjusted on HCF characteristics (public or private) and activity. RESULTS: The analysis was performed on 4062 (48,2%) observations after exclusion of HCF not concerned by the ICATB public reporting indicator (7.2% of observations), invalid or missing data (21,2% of observations) and irrelevant values (23.4%). The global antibiotic consumption was 343 defined daily doses (DDD) per 1000 patient-days (PD) and varied little between 2006 and 2008. However, the linear regression model showed an increase of 5.7 DDD per 1000 PDs per year (P<0.001). There was a positive association between antibiotic consumption and ICATB score, mainly concerning sub-scores ICATB-action and ICATB-organization. CONCLUSION: The recent lack of decrease in antibiotic consumption in French HCF between 2006 and 2008 is coherent with other available national data, but exclusion of more than 50% of observations limits the impact of this analysis. The relationship between policy of good use and consumption of antibiotics remain difficult to specify, because of the short (three years) study length and because of the nature of ICATB, a composite indicator assessing only partly antibiotic policies.

Antibiotic stewardship programmes: legal framework and structure and process indicator in Southwestern French hospitals, 2005-2008.

French hospitals are required to implement antibiotic stewardship programmes (ABS) to improve antibiotic use. We analysed the legal framework on ABS and assessed its impact on hospitals' ABS development in Southwestern France. For each official text, required measures, date of issue, means of control and incentives were analysed. Annual retrospective surveys were conducted in 84 hospitals from 2005 to 2008 to monitor implementation of ABS components: organisation, resources and actions. Evolution of individual measures and of a structure and process indicator (SPI) reflecting ABS was described for each hospital. From 2002, official texts issued by health authorities set out requirements on ABS, based on previous professional guidelines. Incentives and means of control were reinforced in 2006 and in 2007 with mandatory reporting of SPI for public disclosure. ABS implementation improved during the course of the study period. In 2008, at least 98% of hospitals had implemented formularies, antibiotic committees, surgical prophylaxis guidelines, and monitored antibiotic use; antibiotic advisors were appointed in 85% of hospitals. Little progress was made regarding time dedicated by pharmacists to antibiotic management and restrictive dispensation using stop-orders. Computerised tools, continuing education and audits remained under-used. SPI values were higher in private hospitals and rehabilitation centres than in others. Official texts and the SPI public disclosure increased professionals' and hospital managers' commitment to develop ABS, resulting in improvements. However, some actions still need to be reinforced. It appears crucial to monitor practical implementation to better approach ABS effectiveness and to adapt requirements.

Easily available adjustment criteria for the comparison of antibiotic consumption in a hospital setting: experience in France.

Hospitals in France are encouraged to monitor antibiotic consumption (AbC) and it is known that this differs among hospitals. The aim of the current study was to identify relevant and easily available adjustment criteria for the purpose of benchmarking. We analysed data from 34 public non-teaching hospitals and 43 private hospitals located in south-western France and overseas departments using retrospective data from 2005. This study investigated the relationship between AbC expressed as defined daily doses per 1000 patient-days (DDD/1000 PDs) or per 100 admissions (DDD/100 admissions) and the number of venous central lines, the number of episodes of bacteraemia and various hospital characteristics. The relationship was tested using multiple linear analyses. The median total AbC in public hospitals was 395 DDD/1000 PDs (range, 196-737) and 341 DDD/100 admissions (range, 180-792). In private hospitals this was 422 DDD/1000 PDs (range, 113-717) and 212 DDD/100 admissions (range, 38-510). The best model for public hospitals included the proportion of PDs in surgery, intensive care and medical wards and explained 84% of the variability in AbC expressed as DDD/1000 PDs. For private hospitals, the mean length of stay and the proportion of PDs in surgery and medical wards explained 68% of the variability in AbC expressed as DDD/100 admissions. Overall, this French experience shows that relevant adjustment criteria for the comparison among hospitals are easily available. It is important that each country establish its own model considering the intrinsic peculiarities of the hospital system and taking into account both indicators (DDD/1000 PDs or DDD/100 admissions) to design the best model.

Relationship between rates of antimicrobial consumption and the incidence of antimicrobial resistance in Staphylococcus aureus and Pseudomonas aeruginosa isolates from 47 French hospitals.

OBJECTIVE: To investigate relationships between rates of antimicrobial consumption and the incidence of antimicrobial resistance in Staphylococcus aureus and Pseudomonas aeruginosa isolates from hospitals. METHODS: We conducted an observational study that used retrospective data from 2002 and linear regression to model relationships. Hospitals were asked to collect data on consecutive S. aureus and P. aeruginosa isolates, consumption rates for antibiotics (ie, anti-infectives for systemic use as defined by Anatomical Therapeutic Chemical class J01), and hospital characteristics, including infection control policies. Rates of methicillin resistance in S. aureus and rates of ceftazidime and ciprofloxacin resistance in P. aeruginosa were expressed as the percentage of isolates that were nonsusceptible (ie, either resistant or intermediately susceptible) and as the incidence of nonsuceptible isolates (ie, the number of nonsuceptible isolates recovered per 1,000 patient-days). The rate of antimicrobial consumption was expressed as the number of defined daily doses per 1,000 patient-days. SETTING: Data were obtained from 47 French hospitals, and a total of 12,188 S. aureus isolates and 6,370 P. aeruginosa isolates were tested. RESULTS: In the multivariate analysis, fewer antimicrobials showed a significant association between the consumption rate and the percentage of isolates that were resistant than an association between the consumption rate and the incidence of resistance. The overall rate of antibiotic consumption, not including the antibiotics used to treat methicillin-resistant S. aureus infection, explained 13% of the variance between hospitals in the incidence of methicillin resistance among S. aureus isolates. The incidence of methicillin resistance in S. aureus isolates increased with the use of ciprofloxacin and levofloxacin and with the percentage of the hospital's beds located in intensive care units (adjusted multivariate coefficient of determination [aR(2)], 0.30). For P. aeruginosa, the incidence of ceftazidime resistance was greater in hospitals with higher consumption rates for ceftazidime, levofloxacin, and gentamicin (aR(2), 0.37). The incidence of ciprofloxacin resistance increased with the use of fluoroquinolones and with the percentage of a hospital's beds located in intensive care ( aR(2), 0.28). CONCLUSIONS: A statistically significant relationship existed between the rate of fluoroquinolone use and the rate of antimicrobial resistance among S. aureus and P. aeruginosa isolates. The incidence of resistant isolates showed a stronger association with the rate of antimicrobial use than did the percentage of isolates with resistance.

Outbreak of staphylococcal bullous impetigo in a maternity ward linked to an asymptomatic healthcare worker.

An outbreak of staphylococcal bullous impetigo occurred over a period of five months in a maternity ward involving seven infected and two colonised neonates. The skin lesions were due to epidermolytic toxin A-producing Staphylococcus aureus. Infection control measures were implemented and a retrospective case-control study performed. Contact with an auxiliary nurse was the only risk factor for cases of bullous impetigo (P<0.01). The nurse cared for all seven cases and was an asymptomatic nasal carrier of the epidemic strain. Repeated courses of decontamination treatment failed to eradicate carriage. Nine months after the last case, another neonate developed a more severe form of bullous impetigo and the auxiliary nurse was reassigned to an adult ward.

Determinants of glycopeptides consumption in hospitals.

The aim of this study was to describe consumption of glycopeptides and to study factors associated with their use in 47 French hospitals. Consumption of glycopeptides for systemic use (defined daily doses per 1,000 patient-days: DDD/1,000 PD and per 100 admissions), number of methicillin-resistant Staphylococcus aureus (MRSA) (percentage and incidence per 1,000 patient-days), and number of venous central lines and hospital characteristics (size, length of stay, number of beds: total and for each hospital inpatient areas and antibiotic policies) were recorded from January, 2002, through December, 2002. Multiple linear regression was performed to check for hospital characteristics. The median rate of total consumption of glycopeptides was 4.11(range 0.21-27.22) DDD per 1,000 PD with higher consumption in large public hospitals and in intensive care areas (median 46.51; range 7.19-134) than in surgery areas (median 4.5; range 0.17-24.76). The consumption of glycopeptides correlated with MRSA incidence, but not with the proportion of MRSA. In the multivariate analysis, the incidence of MRSA and the number of beds in surgery areas were independent predictors of total glycopeptides use in the hospital, expressed in DDD per 1,000 PD (R2 adjusted, 0.39). The incidence of MRSA, the number of venous central lines, and the number of beds in the medicine areas were significant determinants associated with higher consumption of glycopeptides expressed in DDD per 100 admissions (R2 adjusted, 0.73). To reduce glycopeptides use in hospitals, the first effort required is that hospitals focus increased attention on the prevention of cross transmission for MRSA between patients but also on the use of the venous central line. Furthermore, hospitals have to compare their data with others to identify overuse of glycopeptides and to plan control interventions.

[Relationship between antibiotic policies and antibiotic consumption in hospitals]. / Relation entre politique de bon usage et consommation des antibiotiques dans les établissements de santé.

OBJECTIVE: The authors had for aim to study the relationship between antibiotic policies and antibiotic consumption in hospitals. DESIGN: A component analysis was used to summarize the various measures of the antibiotic policies developed by hospitals. Antibiotics consumption was expressed as a number of Daily Defined Doses per 1,000 patient-days. The relation was studied by a multiple linear regression model with adjustment on hospital activity. RESULTS: The first component illustrated an active program of antibiotic policies associating: a local antibiotic committee, an infectious diseases consultant, written local guidelines for prescriptions and restrictive measures before dispensing. The highest antibiotic consumption was associated with active policies, especially for carbapenems, glycopeptides, and aminoglycosides. However the relationship differed according to the type of hospital, with lower antibiotic consumption, especially for penicillins, in private hospitals that had more active policies. CONCLUSION: The difference between public and private hospitals could be explained by the type of institution but also by the unit used to measure antibiotic consumption.

[Policies for the use of antibiotic in 99 Southwestern French hospitals in 2002]. / Politique d'utilisation des antibiotiques: état des lieux dans 99 établissements de santé de l'interrégion Sud-Ouest.

OBJECTIVE: Increasing antimicrobial resistance in bacteria is a major health problem and requires the implementation of stringent policies to optimize the use of antibiotics. DESIGN: In 2003 the authors conducted a study in southwestern French hospitals, using a questionnaire to assess the implementation of antibiotic policies according to national guidelines issued by the French government in 2002. RESULTS: The most frequent actions quoted by the 99 respondents were: issuing of a list of available antibiotics, issuing of information regarding antibiotic consumption and bacterial resistance, and control of antibiotics dispensation. Local guidelines were available in 45% of hospitals for curative treatment and in 87% for antibioprophylaxis in surgery. The evaluation of antibiotic use and computer links between clinical settings, pharmacy and microbiology lab were the less widespread measures. The number and type of actions were related to hospital size and activity. CONCLUSIONS: These findings support that policies for an appropriate use of antimicrobials should be reinforced by issuing treatment guidelines and specific tools for dispensation and evaluation. This survey also emphasizes the need for appropriate policies relating to the size and medical activities of healthcare institutions.

[Endoscopes in urology: disinfection, sterilization, labeling and tracking. Circulars and decrees. Modes of application and commentary. The Committee of Infectious Diseases of the French Association of Urology. Congressional forum UFA--Paris, November 1996. DGS Circular 20 October 1997]. / Les endoscopes en urologie: désinfection, stérilisation, marquage et traçage. Circulaires et décret. Modalités d'application et commentaires. Comité d'infectiologie de l'Association Française d'Urologie (CIAFU). Forum Congrès AFU-Paris, novembre 1996. Circulaire DGS 20 octobre 1997.

Administrative texts published in 1995, 1996 and 1997, have reinforced materiovigilance and impose disinfection precautions for endoscopes. The steps of disinfection of non-sterilizable endoscopes are: preliminary treatment, rinsing, actual disinfection, final rinsing, storage (see: Progrès en Urologie, 1997, 7, 505-507). Each procedure from collection of the endoscope until storage must be defined by written standard operating procedures validated by CLIN. The risk of transmission of Creutzfeld-Jakob disease requires autoclaving, which is only possible, at the present time, with the most recent rigid endoscopes. Until disinfection has become generalized, the traceability of endoscopes (labelling, utilization files) must be established on the model recommended for haemovigilance (circular of 02/04/96).

[Rules of decontamination and disinfection of medicosurgical instruments in the operating room]. / Règles de décontamination et de désinfection du matériel médico-chirurgical au bloc opératoire.

Nosocomial infections may result from the reuse of surgical devices if adequate disinfection or sterilization measures are not employed. The first step of reprocessing occurs immediately after use in the operating room. This consists of cleaning and decontamination to eliminate organic material and to reduce the number of microorganisms, in order to protect personnel who subsequently manipulate these instruments and to facilitate the ultimate process of sterilization or disinfection. Instruments that cannot be sterilized must be submitted to "high level disinfection" to remove undesirable microorganisms. In order to guarantee the desired results of disinfection, it is very important to adopt reliable and effective protocols, chemical products with good germicidal properties and with minimal adverse effects on the personnel and the environment. The personnel involved in this delicate and important task must be thoroughly trained. If the above conditions are met, the infectious risk associated with reuse of surgical devices can be controlled.

[The epidemiological surveillance network for nosocomial invasive aspergillosis of the Assistance Publique-Hôpitaux de Paris]. / Le réseau de surveillance épidémiologique de l'aspergillose invasive nosocomiale de l'Assistance Publique-Hôpitaux de Paris.

Since January 1990, a epidemiology surveillance network has been set up by the Paris hospitals for nosocomial invasive aspergillosis. The network includes 39 high risk clinics (haematology, bone marrow graft, organ transplantation) in 19 hospitals. Over the first 3 years of surveillance (1990-1992), 132 cases of aspergillosis have been registered as probably invasive and nosocomial. The incidence of nosocomial invasive aspergillosis invasive aspergillosis has been estimated at 1.16 per 1,000 patient-days in haematology wards, at 4.56% in bone marrow graft and at 1.57 in liver transplantation. Mortality was 57% for all cases registered and 75% for bone marrow transplant patients; 97% of these patients were immunodepressed. Room air filtration with an absolute filter system had been installed for only 32% of the patients at diagnosis of invasive nosocomial aspergillosis. Work areas were in the environment of 68% of the cases reported. Surveillance led to the establishment of incidence and mortality data and emphasized the importance of the problem in terms of public health. In addition, three main elements were recognized concerning the disease: the number of immunodepressed patients in increasing in the hospitals, room air filtration equipment is inadequate, unavoidable work areas in hospitals have a significant effect. A practical guide for the prevention of invasive nosocomial aspergillosis in case of work areas in the hospital was published in 1993. Nevertheless, the proposed measures must be integrated into a global prevention strategy to eliminate sources of contamination and improve food facilities, architecture, air conditioning, internal organization and personnel training in high risk clinics.

Improved column-switching liquid chromatographic method for the determination of the enantiomers of mefloquine.

A liquid chromatographic method for the determination of the enantiomers of mefloquine has been improved. The chromatography involved two columns: an achiral cyanopropyl stationary phase for the quantification of (+/-)-mefloquine and a chiral naphthyl-urea stationary phase for the determination of the enantiomeric ratio. Compared with the previous method, which needed two detectors, this one used one detector-integrator to which the two columns are connected alternately by an automated column-switching system. The method is suitable for the quantification (0.05 microgram/ml) of mefloquine and the determination of enantiomeric ratios from 500-microliters plasma samples with ultraviolet detection.