Application of guidelines for aminoglycosides use in French hospitals in 2013-2014.

In 2011, the French Agency for Safety of Health Products issued guidelines underlining the principles of proper aminoglycosides' use. The aim of the survey was to evaluate adherence to these guidelines two years after their issue. Characteristics of patients receiving aminoglycosides were recorded by voluntary facilities during a 3-month survey in 2013-2014. The modalities of aminoglycosides treatment were analysed by comparison with the French guidelines. A total of 3,323 patients were included by 176 facilities. Patients were mainly hospitalized in medical wards (33.0%), and treated for urinary-tract infections (24.7%). Compliance regarding the clinical indication and the daily aminoglycosides dose was observed in 65.2% and 62.9% of the cases, respectively. A 30-min once-daily IV administration was recorded in 62.5% of the cases. Aminoglycosides treatment duration was appropriate (≤5 days) for 93.6% of the patients. When considering the four criteria together, 23.2% of the patients had a treatment regimen aligned with the guidelines. Requests for measurements of peak and trough AG serum concentrations matched the guidelines in 24.9% and 67.4% of the cases, respectively. Two years after guidelines issue, aminoglycosides use remains unsatisfactory in French health-care facilities. Efforts should be made for guidelines promotion, especially regarding the issue of underdosing.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test]. / Conduite à tenir devant une anomalie biologique découverte lors du bilan pré-don cellules souches hématopoïétiques: sérologie IgM positive pour le cytomégalovirus, le virus d'Epstein-Barr, la toxoplasmose, ou la syphilis.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis IgM positive serology test.

[How to handle unexpected biological abnormalities observed in the pre-donation workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre-transplant positive pregnancy test and monoclonal gammapathy]. / Conduite à tenir devant un problème du donneur de cellules souches hématopoïétiques: test de grossesse positif et gammapathie monoclonale.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. Here we report our results and recommendations regarding the management of common issues related to the donor: pre-transplant pregnancy and monoclonal gammopathy.

Factors associated with recurrence of catheter-related bloodstream infections in home parenteral nutrition patients.

Blood cultures from outpatients receiving home parenteral nutrition (HPN) via long-term central venous access (CVA) were retrospectively analyzed from January 2003 to May 2009. When infection of the CVA was not due to Staphylococcus aureus, Pseudomonas aeruginosa, or Candida, catheter salvage was attempted for a maximum of three consecutive infections on the same CVA. Factors influencing the time-to-next-infection were studied, whether the catheter was changed after the last infection or not. Neither the McCabe score, age, history of cancer, diabetes mellitus nor immunosuppression, curative antibiotic lock, type of bacteria, type or duration of treatment had an influence on the time-to-next-infection. The time-to-next-infection was significantly associated with the status of CVA (saved or changed) and its type (tunneled catheter with or without a cuff, or implanted port catheter).

Impact of combination therapy with aminoglycosides on the outcome of ICU-acquired bacteraemias.

Pharmacodynamic studies report on the rapid bactericidal activity of aminoglycosides, conferring them as being of theoretical interest for bacteraemia treatment. We assessed this issue in a retrospective study of patients with intensive care unit (ICU)-acquired bacteraemias. To determine the impact of aminoglycosides in antimicrobial combination on the outcome of patients with bacteraemia, we performed a monovariate analysis and a logistic regression analysis comparing patients treated with or without aminoglycosides. Forty-eight bacteraemias in 48 patients were included. Eighteen patients received aminoglycosides. Baseline characteristics as well as adaptation and adequation of antibiotherapy did not differ in patients who did or did not receive aminoglycosides. Patients who received aminoglycosides had longer time alive away from the ICU (11.3 ± 8.9 (10 [0-20]) vs. 3.2 ± 6.6 (0 [0-2] days; p = 0.002) and free from mechanical ventilation (12.5 ± 9.3 (14 [0-21] vs. 5.5 ± 9.2 (0 [0-10] days; p = 0.02) on day 28. The ICU mortality was 16% in the aminoglycoside group versus 46% (p = 0.03). In the multivariate analysis, patients treated with aminoglycosides were 6 times less likely to die than those treated without aminoglycosides (confidence interval [CI] = [1.3-28.9]; p = 0.02). Our study supports the hypothesis that combination short-term antibiotherapy with an aminoglycoside for ICU-acquired bacteraemias could increase survival.

A survey on the use of gentamicin in infective endocarditis.

US and European guidelines recommend a daily divided gentamicin dose (3 mg/kg in two or three equally divided doses) for the treatment of infective endocarditis caused by staphylococci or enterococci, but once-daily dosing (3 mg/kg/day) is recommended for streptococcal endocarditis. However, studies have recommended the use of higher doses of gentamicin (4 or ≥5 mg/kg/day) administered once-daily. A survey was conducted in France by mailing a questionnaire to the 595 members of the French Infectious Disease Society regarding their gentamicin prescription patterns in infective endocarditis, focusing on the dosing regimen. The survey was answered by 137 physicians (23%). The proportions of physicians following guideline-based regimens were similar for each organism (30.9%, 38.8%, and 39.4% for staphylococci, enterococci, and streptococci, respectively [p=0.26]). In contrast, the proportions of physicians following literature-based regimens were significantly different for each organism (59.6%, 42.5%, and 27.7% for staphylococci, enterococci, and streptococci, respectively [p<0.001]). The number of years practicing and the type of practice (university vs. non-university hospital) did not influence the gentamicin dose or regimen. Although adherence to published guidelines for gentamicin administration in patients with infective endocarditis was poor, a large proportion of physicians who did not follow those guidelines used literature-based regimens.

Explicit definitions of potentially inappropriate prescriptions of antibiotics in hospitalized older patients.

CONTEXT: The use of explicit definitions of potentially inappropriate prescriptions of antibiotics (antibiotic PIPs) might constitute an innovative means to fight against antimicrobial resistance. Explicit definitions of PIPs can reduce the rate of inappropriate prescriptions, but explicit definitions of antibiotic PIPs in geriatric medicine are currently lacking. The objective of the study was to develop explicit definitions of antibiotic PIPs for hospitalized older patients. METHOD: We performed a qualitative study of focus groups involving geriatricians and infectious disease specialists. The study complied with the Consolidated Criteria for Reporting Qualitative Research. Transcripts of audio recordings were analyzed in a two-step independent reviewing process. The exact wording of the definitions was validated by a steering committee, an independent expert group, and the focus group participants. RESULTS: The four focus groups comprised 28 stakeholders. Our analysis identified 65 explicit definitions of antibiotic PIPs: 47 (73%) concerned misuse, 15 (23%) concerned overuse and three (5%) concerned underuse. Most definitions were related to critically important antibiotics: 11 (17%) for fluoroquinolones, eight (12%) for amoxicillin-clavulanic acid, eight (12%) for cephalosporins, seven (11%) for aminoglycosides, and five (8%) for carbapenems. CONCLUSION: To address the public health challenge of antimicrobial resistance, our study generated explicit definitions for antibiotic PIPs in older patients. We intend to refine and to validate these definitions through a national Delphi survey; the resulting consensus might provide key messages for prescribers and open up perspectives for reducing the incidence of antibiotic PIPs.

Invasive fungal infections: epidemiology and analysis of antifungal prescriptions in onco-haematology.

WHAT IS KNOWN AND OBJECTIVE: Invasive fungal infections (IFI) are associated with high rates of morbidity and mortality, particularly in onco-haematology patients. We aimed to study the epidemiology of IFI in neutropenic patients and estimate the economic impact of treatment of those infections. METHODS: All patients hospitalized in onco-haematology, and treated with antifungal agents, in 2005 were investigated. Four features were studied: the diagnosis for each patient, the antifungal drugs used, the thoracic densitometry reports and the sero-mycological data. Infectious episodes were stratified according to the EORTC 2008 classification criteria (10). RESULTS AND DISCUSSION: Of the 1130 patients surveyed, 192 patients received systemic antifungal agents. Of these 46% had acute leukaemia, 29% bone-marrow allografts, 7% lymphoma and 18% other malignant haemopathies. Using the EORTC 2008 criteria (10), there were 8 proved IFI (3 aspergillosis, 3 candidosis and 2 other IFI), 17 probable IFI (11 aspergillosis, 6 candidosis) and 16 possible aspergillosis. The incidence of IFI was 2·1%. Eighty patients (41·7%) had received prophylaxis: 56 with fluconazole and 24 with voriconazole. Treatment was most often empirical (n = 127, 66·1%). Combination of two antifungals was used in 17 cases. The mean duration of prophylactic, empirical, proved/probable aspergillosis-directed, candidaemia-directed and combination treatment was 19, 19, 46, 32 and 27 days, respectively. The cost of antifungal treatment in 2005 reached almost 2,000,000 €, including 427,000 € for documented infections (proved and probable), 1,246,000 € for empirical treatment and 58,300 € for prophylaxis. WHAT IS NEW AND CONCLUSION: The incidence of IFI is low but the pharmacoeconomic impact is extremely high. Improved strategies are required to reduce the frequency and duration of empirical treatment without compromising beneficial outcome.

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.

Antibiotics and chronic kidney disease: Dose adjustment update for infectious disease clinical practice.

Antibiotic prescription in chronic kidney disease patients poses a twofold problem. The appropriate use of antibacterial agents is essential to ensure efficacy and to prevent the emergence of resistance, and dosages should be adapted to the renal function to prevent adverse effects. SiteGPR is a French website for health professionals to help with prescriptions to chronic kidney disease patients. A working group of infectious disease specialists and nephrology pharmacists reviewed the indications, dosing regimens, administration modalities, and dose adjustments of antibiotics marketed in France for patients with renal failure. Data available on the SiteGPR website and detailed in the present article aims to provide an evidence-based update of infectious disease recommendations to health professionals managing patients with chronic kidney disease.

Exogenous acquisition of Pseudomonas aeruginosa in intensive care units: a prospective multi-centre study (DYNAPYO study).

BACKGROUND: Pseudomonas aeruginosa remains one of the most common nosocomial pathogens in intensive care units (ICUs). Although exogenous acquisition has been widely documented in outbreaks, its importance is unclear in non-epidemic situations. AIM: To elucidate the role of exogenous origin of P. aeruginosa in ICU patients. METHODS: A chronological analysis of the acquisition of P. aeruginosa was performed using samples collected in 2009 in the DYNAPYO cohort study, during which patients and tap water were screened weekly. Molecular relatedness of P. aeruginosa isolates was investigated by pulsed-field gel electrophoresis. Exogenous acquisition was defined as identification of a P. aeruginosa pulsotype previously isolated from another patient or tap water in the ICU. FINDINGS: The DYNAPYO cohort included 1808 patients (10,402 samples) and 233 water taps (4946 samples). Typing of 1515 isolates from 373 patients and 375 isolates from 81 tap water samples identified 296 pulsotypes. Analysis showed exogenous acquisition in 170 (45.6%) of 373 patients. The pulsotype identified had previously been isolated from another patient and from a tap water sample for 86 and 29 patients, respectively. The results differed according to the ICU. CONCLUSION: Exogenous acquisition of P. aeruginosa could be prevented in half of patients. The overall findings of this survey support the need for studies on routes of transmission and risk assessment approach to better define how to control exogenous acquisition in ICUs.

Adult community-acquired bacterial meningitis requiring ICU admission: epidemiological data, prognosis factors and adherence to IDSA guidelines.

Numerous guidelines are available to guide empirical antimicrobial therapy (EAT) in acute bacterial meningitis (ABM) patients. We analysed prognosis factors and compliance to the Infectious Diseases Society of America (IDSA) guidelines in ABM patients requiring stay in an intensive care unit (ICU). A 10-year retrospective study, using prospectively collected data, in 82 ABM patients admitted to a 16-bed university-affiliated French ICU was undertaken. Seventeen patients (20.7%) died during ICU stay. Multivariate analysis isolated four factors associated with in-ICU death: alcoholism (P = 0.007), acute kidney injury (P = 0.006), age >60 years (P = 0.006) and ICU admission for neurological failure (P = 0.01). Causative pathogens were isolated for 62 (75.6%) patients, including 29 pneumococci, 14/28 of which were non-susceptible to penicillin. No characteristics, particularly recent hospitalisation and/or antibiotic delivery, was associated with penicillin susceptibility. Compliance to IDSA guidelines was 65%. Non-compliance concerned to be essentially the non-delivery or low dosage of vancomycin. Treatment compatible with IDSA guidelines was associated with a decreased ICU mortality in univariate (61.5% survival vs. 35.3%, P = 0.05) but not in multivariate analysis. In-ICU mortality associated with ABM remains high. Prognosis factors are related to the severity of disease or underlying conditions. Penicillin non-susceptible Streptococcus pneumoniae can occur without any of the usual predisposing factors.

Prospective evaluation of the management of urinary tract infections in 134 French nursing homes.

OBJECTIVE: Prospective assessment of the management of urinary tract infections (UTI) in the nursing homes of the Hauts-de-France region. PATIENTS AND METHODS: A 50-question form had to be filled in for up to five consecutive residents treated for UTI in each nursing home. If necessary, diagnoses were reclassified according to the 2014 French Infectious Diseases Society guidelines. Analyses were presented per supposed (reported) and reclassified diagnoses. RESULTS: Of 397 contacted facilities, 134 participated and informed 444 UTI episodes. Reported diagnostic criteria were burning urination (32%), malodorous urine (29%), confusion (28%), and turbid urine (19%). Twenty-one percent of diagnoses were based on erroneous criteria. Less than 50% of residents had a urine dipstick test performed and 94% a urine culture. The main pathogen was Escherichia coli. Reported indications were uncomplicated cystitis (32%), unspecified UTI (26%), complicated cystitis (9%), while no reason was given in 25% of cases. Only 10% of diagnoses were consistent with the guidelines: complicated cystitis (49%), asymptomatic bacteriuria (21%), acute pyelonephritis (21%), male UTI (9%). Almost 85% of prescriptions were active on the isolated bacteria. The empirical antibiotic therapy was consistent with the diagnosis in 16% of cases (30% for reclassified diagnoses). The two most prescribed antibiotic classes were fluoroquinolones (22.1%) and oral third-generation cephalosporins (19.1%). Only two of 157 possible de-escalations were performed. Duration of treatment was adequate for 19% of UTIs (9.6% of reclassified cases). CONCLUSION: Our study revealed multiple deficiencies in diagnosis, antibiotic choice, treatment duration, and reevaluation.

Use of 27 parenteral antimicrobial agents in north of France hospitals.

BACKGROUND: Little data are available on antibiotic (AB) use in French hospitals. METHODS: 1995-2001 annual data on WHO defined daily doses (DDD) and hospitalization days (HD) were collected from volunteer hospitals. Twenty-three AB (amikacin, aztreonam, cefepime, cefotaxime, cefpirome, ceftazidime, ceftriaxone, ciprofloxacin, fosfomycin, fusidic acid, levofloxacin, imipenem, isepamicin, ofloxacin, pefloxacin, piperacillin, piperacillin/tazobactam, quinupristin/dalfopristin, sulbactam, teicoplanin, ticarcillin, ticarcillin-clavulanic acid, vancomycin) and four antifungals (amphotericin B lipid formulations, caspofungin, and fluconazole) were surveyed. Antimicrobial use was expressed as the number of DDD per 1000 HD. RESULTS: Fifty-eight hospitals participated in the 2001 study. AB consumption was higher in hospitals with > 400 acute care beds (214.8 +/- 116 DDD/HD) than in 200-400 beds hospitals (134.2 +/- 39 DDD/HD) or < 200 beds hospitals (104.3 +/- 74 DDD/HD) P = 0.0005. Wide variations in AB choice and volumes were observed among similar sized hospital. Fifteen hospitals, representing one third of the region's acute care beds, provided complete 7-year data. The use of antibacterials increased 23% from 119.9 to 147.2 DDD per 1000 HD. Most of this increase was due to fluoroquinolones (plus 72%; 17.8 vs. 30.6, P = 0.0068), ceftriaxone (plus 90%; 14.4 vs. 27.4; P < 0.0001), and cefepime (plus 264%; 3.4 vs. 12.2%, P = 0.028). The only decreasing class was aminoglycosides (minus 48%; 27.7 vs. 14.5; P = 0.003). CONCLUSIONS: This data confirms the high level of AB consumption in French hospitals.

Long-term follow up of invasive aspergillosis in allogeneic stem cell transplantation recipients and leukemia patients: Differences in risk factors and outcomes.

Antifungal prophylaxis (AP) has dramatically changed the epidemiology of invasive aspergillosis (IA). To better understand the differences in terms of clinical significance of IA between allogeneic stem cell transplantation (allo-SCT) recipients and patients treated for leukemia, we report a single-center study of 735 unselected consecutive patients treated between 2000 and 2004, before the era of systematic AP. Probable or confirmed IA were observed in 29 patients (2008 EORTC/MSG criteria), including 7/235 undergoing allo-SCT (5.2%), 19/380 treated for acute leukemia (5.0%), 1/116 for chronic lymphocytic leukemia (0.9%) and 2/104 for myelodysplastic syndrome (1.9%). In allo-SCT recipients, IA occurred later than in leukemia patients, after the neutropenic period. The median time between the last treatment and the diagnosis of IA was 231 days (range, 68-341) in allo-SCT recipients and 17 days (6-57) in leukemia patients (P<0.001). Importantly, the 7 cases of IA after allo- SCT occurred only in patients treated with corticosteroids for graft-versus-host disease (GVHD). Mortality directly related to IA was 24%. The 100-day, 2-year and 10-year overall survival were 42.9%, 0%, 0% in allo-SCT recipients compared to 68.1%, 18.2%, 13.6% in leukemia patients, respectively (P≥0.05). These poor outcomes were mainly attributable to non-relapse mortality (NRM). In conclusion, our data allows distinguishing 2 types of IA occurring at different time in the treatment course. In both cases, the NRM is very high and treatment remains challenging. Thus, systematic broad-spectrum AP against Aspergillus should be considered in acute leukemia patients during the neutropenic phase and in all patients undergoing allo-SCT who develop GVHD.

[French recommendations on control measures to reduce the infectious risk in immunocompromised patients]. / Quelles mesures pour maîtriser le risque infectieux chez les patients immunodéprimés ? Recommandations formalisées d'experts.

The increase use of immunosuppressive treatments in patients with solid cancer and/or inflammatory diseases requires revisiting our practices for the prevention of infectious risk in the care setting. A review of the literature by a multidisciplinary working group at the beginning of 2014 wished to answer the following 4 questions to improve healthcare immunocompromised patients: (I) How can we define immunocompromised patients with high, intermediate and low infectious risk, (II) which air treatment should be recommended for this specific population? (III) What additional precautions should be recommended for immunocompromised patients at risk for infection? (IV) Which global environmental control should be recommended? Based on data from the literature and using the GRADE method, we propose 15 recommendations that could help to reduce the risk of infection in these exposed populations.

Tuberculosis treatment duration in France: From guidelines to daily practice.

BACKGROUND: Guidelines for tuberculosis (TB) recommend 6 months of treatment except for meningeal TB, where a 9- to 12-month course may be preferred. METHODS: In order to assess whether practices in France are in agreement with those guidelines, we performed an anonymous audit of the policy of French physicians, focusing on TB treatment duration and corticosteroid use according to the TB presentation. RESULTS: Sixty-six completed forms were analyzed. Reported treatment duration was usually 6 months for pulmonary TB (91% of physicians) and miliary TB (45%), 9 months for pulmonary TB in HIV-infected patients (42%) and for TB lymphadenitis (57%), and 12 months for TB meningitis (79%) and osteo-articular TB (65%). Corticosteroid use was systematic for meningitis (80%) and pericarditis (65%). CONCLUSION: This study reveals discrepancies between guidelines and daily practice for TB treatment duration in France: We observed a very high reported rate of unnecessary, prolonged treatment for most extrapulmonary TB.

[Physicians referent for antimicrobial therapy in French hospitals. Origins and expectations. A French infectious diseases society survey]. / Origine et attente des référents antibiotiques dans les établissements de santé en France. Résultats d'une enquête de la SPILF.

The French Infectious Diseases Society (SPILF) conducted a web-based survey of physicians' referent for antimicrobial therapy (ABT). The 106 respondents came mostly from public (95%) big (median 815 beds) hospitals. A referent according to health ministry requirements was identified in 88 hospitals. In, 18 others, a physician performed the job without identification per se. This activity had a specific financing in only 12% of cases. Two thirds of the referents were infectious diseases physicians, the others had for training a university degree in ABT. Expectations about SPILF were mostly implementation of good practices of ABT (73%), organization of CME sessions (61%), a referent dedicated session during the annual SPILF meeting (58%), a SPILF driven certification (58%) and the creation of regional networks of referents (55%). Implementing a training and evaluation program for ABT referents becomes a priority for the SPILF.

[Pulmonary zygomycosis in a patient treated for invasive aspergillosis]. / Zygomycose pulmonaire chez un patient traité pour une aspergillose invasive possible.

We report a pulmonary mucormycosis due to Absidia corymbifera. It occurred in a leukemic patient treated for a probable aspergillosis regressing after voriconazole treatment. The patient responded to surgery and a combination of liposomal amphotericin B and itraconazole. He was alive and well after 7-months of follow up.