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.

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.

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.

[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.

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.

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.

Evaluating the management of 493 patients presenting with bacteremia in 23 northern French hospitals.

OBJECTIVES: We aimed to update the epidemiology of bacteremia and evaluate their management and short-term outcome. METHODS: We conducted a prospective multicenter survey from October to November 2011. Consecutive patients with at least one positive blood culture (BC) were included in the study. We evaluated the type and adequacy of empirical and documented antibiotic therapy, time to active antibiotic therapy, compliance with guidelines, and 10-day outcome. RESULTS: A total of 23 public and private hospitals and 633 patients (493 true pathogens and 140 contaminants) were included in the study. Patients' wards were medicine (57%), surgery (19%), intensive care (14%), onco/hematology (3.7%), pediatrics (3.4%), infectious diseases (1.8%), and obstetrics (1.2%). Main pathogens were Escherichia coli (36%), Staphylococcus aureus (16%), coagulase-negative staphylococci, and Klebsiella sp. (8% each). A total of 43 (8.7%) multidrug-resistant strains were observed, including 26 extended-spectrum beta-lactamase strains and 15 methicillin-resistant S. aureus strains. An antibiotic active against the isolated pathogen was used in 74% of empirical and 96% of documented therapies. Median time between BC and administration of an active drug was 0.61 day. Empirical antibiotic therapies were protocol-compliant in 77% of cases. Few (4%) patients with contaminated BC received an antibiotic therapy (all inappropriate). Day-10 mortality was 12.1%, higher in patients presenting with severe sepsis or septic shock (22.5%) than in patients presenting with non-severe bacteremia (7.1%; P<0.0001). CONCLUSION: The management of bacteremia seems satisfactory in these volunteer hospitals but bacteremia remains a severe infection.

Antibiotic use and good practice in 314 French hospitals: The 2010 SPA2 prevalence study.

OBJECTIVES: We aimed to assess antibiotic prescriptions to identify potential targets for improvement. METHODS: We conducted a point prevalence survey (November 2010) of antibiotic use in 314 voluntary hospitals recruited by the French Infectious Diseases Society (SPILF) and the National Observatory for Epidemiology of Bacterial Resistance to Antimicrobials (ONERBA). Data were entered online, immediately analyzed and exported. RESULTS: The prevalence of antibiotic use was 19.5% (9059/46,446patients). A higher prevalence was observed in the infectious disease (58.4%), hematology (58%), and intensive care (48.7%) units. The three most frequently used antibiotic classes were aminopenicillins (23.8%), fluoroquinolones (17.9%), and 3rd-generation cephalosporins (16.7%). A monotherapy was prescribed to 64% of patients. The reasons for the antibiotic prescription were written in the medical records of 74% of patients and 62% were consistent with the local guidelines. CONCLUSION: Our results are similar to that of other studies. Various local targets for improvement have been identified to help hospitals define a better antibiotic stewardship.

Risk factors for Pseudomonas aeruginosa acquisition in intensive care units: a prospective multicentre study.

BACKGROUND: Pseudomonas aeruginosa is a major nosocomial pathogen in intensive care units (ICUs); however, endogenous versus exogenous origin of contamination remains unclear. AIM: To identify individual and environmental ICU risk factors for P. aeruginosa acquisition. METHODS: A five-month prospective multicentric study was performed in ten French ICUs. Adult patients hospitalized in ICU for ≥ 24 h were included and screened for P. aeruginosa colonization on admission, weekly and before discharge. P. aeruginosa acquisition was defined by a subsequent colonization or infection if screening swabs on admission were negative. Water samples were obtained weekly on water taps of the ICUs. Data on patient characteristics, invasive devices exposure, antimicrobial therapy, P. aeruginosa water and patient colonization pressures, and ICU characteristics were collected. Hazard ratios (HRs) were estimated using multivariate Cox model. FINDINGS: Among the 1314 patients without P. aeruginosa on admission, 201 (15%) acquired P. aeruginosa during their ICU stay. Individual characteristics significantly associated with P. aeruginosa acquisition were history of previous P. aeruginosa infection or colonization, cumulative duration of mechanical ventilation and cumulative days of antibiotics not active against P. aeruginosa. Environmental risk factors for P. aeruginosa acquisition were cumulative daily ward 'nine equivalents of nursing manpower use score' (NEMS) [hazard ratio (HR): 1.47 for ≥ 30 points; 95% confidence interval (CI): 1.06-2.03] and contaminated tap water in patient's room (HR: 1.76; CI: 1.09-2.84). CONCLUSION: Individual risk factors and environmental factors for which intervention is possible were identified for P. aeruginosa acquisition.

Management and control of a carbapenem-resistant Acinetobacter baumannii outbreak in an intensive care unit.

OBJECTIVE: We had for aim to describe the identification and management of a 14-clonal carbapenem-resistant Acinetobacter baumannii (CRAB) outbreak, following admission of a known CRAB-infected patient in an ICU. METHODS: We reviewed the carriers' files and outbreak management procedures. RESULTS: The index patient was admitted with strict isolation precautions. The outbreak started 2 months after his discharge. It persisted despite reinforcement of strict isolation precautions, staff and patient cohorting, and extensive environmental decontamination including 2 rounds of routine terminal cleaning and disinfection or 1 round of cleaning and disinfection followed by hydrogen peroxide treatment. A second epidemic peak, after 4 weeks without any case, led to another wide environmental sampling and decontamination rounds. The source of the CRAB outbreak was suspected to be the blood pressure cuffs Velcro. Switching to cuffs submersible in a disinfectant stopped the outbreak. CONCLUSIONS: CRAB outbreaks are difficult to manage and sources of persistent colonization can be unexpected.

Feedback on difficulties raised by the interpretation of serological tests for the diagnosis of Lyme disease.

OBJECTIVES: We had for objectives: i) to evaluate the accuracy of serologic testing for Lyme borreliosis performed in a private medical laboratory (PML); ii) to evaluate the impact of these tests on the practices of infectious diseases specialists (IDS). PATIENTS AND METHOD: This study was performed in two steps: i) retrospective study of patients followed in a university hospital infectious diseases outpatient clinic for suspected Lyme borreliosis, tested (ELISA and Western blot) by both the PML and the National Reference Center (NRC); ii) national survey on IDS practices concerning patients consulting for suspected Lyme borreliosis. RESULTS: Between July 2008 and July 2011, 128 patients consulting for suspected Lyme borreliosis were tested by both laboratories. Serological tests came back positive in 91% of cases from the PML versus 8% of cases from the NRC. Lyme borreliosis was the IDS's final diagnosis for 3.6% of patients. The survey on practices revealed that: i) the modal duration of consultation for suspected Lyme borreliosis was 30-60 minutes; ii) for 33% of patients, serologic test results performed at the PML were the only reason to suspect Lyme borreliosis; iii) 60% of patients had no indication for antibiotics. CONCLUSION: The serological test performed in the PML were positive most of the time, but were not confirmed by tests performed at the NRC. This discrepancy lead to multiple and prolonged consultations in infectious diseases clinics, and discordance in the indications for antibiotics.

Antifungal stewardship: implementation in a French teaching hospital.

CONTEXT: Invasive fungal infections are responsible for severe morbidity and mortality in immunocompromised patients. New, more effective antifungal drugs have been available for more than a decade but are extremely expensive suggesting the need for judicious prescribing. INTERVENTION: Infectious diseases physicians had been closely collaborating with hematologists on antimicrobial use since 2000. In 2002, an antifungal stewardship program (ASP) was implemented. It included discussing antifungal prescriptions with a dedicated infectious diseases physician twice weekly, telephone counseling 5 days a week from 9 A.M. to 7 P.M., and training meetings for junior/senior prescribers organized at least once yearly. The same year, a multidisciplinary group drafted evidence-based local guidelines on the use of antifungals in the hematology unit, which were published in 2004. These guidelines included decision algorithms and preprinted prescription forms that allowed only guideline-recommended drugs for a given indication. These guidelines have been updated and simplified at least every 2 years (current version 7.0; 2012). RESULTS: Between 2003 and 2012, in the 20-bed isolated hematology sector (allograft and acute leukemia induction chemotherapy patients), antifungal consumption decreased by 40% (from approximately 1000 to 620 defined daily doses per 1000 hospitalization days). Invasive fungal infections (IFI) remained stable in the whole 51-bed department, during the study period, with 1 to 2 IFI per month. In 2005, the 12-week survival rate for 29 cases of invasive aspergillosis was 72%. Early IFI related mortality has decreased recently. CONCLUSION: A permanent collaboration between hematologists and an infectious diseases physician can improve antifungal prescribing.