Trends in Antibiotic Consumption and Resistance in France Over 20 Years: Large and Continuous Efforts but Contrasting Results.

BACKGROUND: Antimicrobial resistance (AMR) is a serious threat to humanity. This paper describes the French efforts made since 2001 and presents data on antimicrobial consumption (AC) and AMR. METHODS: We gathered all data on AC and AMR recorded since 2001 from different national agencies, transferred on a regular basis to standardized European data on AC and resistance in both humans and animals. RESULTS: After a large information campaign implemented in France from 2001 to 2005 in humans, AC in the community decreased significantly (18% to 34% according to the calculation method used). It remained at the same level from 2005 to 2010 and increased again from 2010 to 2018 (8%). Contrasting results were observed for AMR. The resistance of Staphylococcus aureus decreased significantly. For gram-negative bacilli, the results were variable according to the microorganism. The resistance of Enterobacteriaceae to third-generation cephalosporins increased, remaining moderate for Escherichia coli (12% in 2017) but reaching 35% in the same year for Klebsiella pneumoniae. Resistance to carbapenems in those 2 microorganisms remained below 1%. Both global AC and resistance to most antibiotics decreased significantly in animals. CONCLUSIONS: Antibiotic consumption decreased significantly in France after a large public campaign from 2001 to 2005, but this positive effect was temporary. The effect on AMR varied according to the specific microorganism: The effect was very impressive for gram-positive cocci, variable for gram-negative bacilli, and moderate for E. coli, but that for K. pneumoniae was of concern. The consumption of and resistance to antibiotics decreased significantly in animals.

Management and outcome of bloodstream infections: a prospective survey in 121 French hospitals (SPA-BACT survey).

BACKGROUND: Bloodstream infections (BSIs) are severe infections that can be community or hospital acquired. Effects of time to appropriate treatment and impact of antimicrobial management team are discussed in terms of outcome of BSI. We sought to evaluate the impact of initial BSI management on short-term mortality. PATIENTS AND METHODS: A prospective, multicenter survey was conducted in 121 French hospitals. Participants declaring BSI during a 1-month period were included consecutively. Data on patient comorbidities, illness severity, BSI management, and resistance profile of bacterial strains were collected. Predictors of 10-day mortality were identified by multivariate regression for overall BSI, health care-related and hospital-acquired BSI. RESULTS: We included 1,952 BSIs. More than a third of them were hospital acquired (39%). Multidrug resistance was identified in 10% of cases, mainly in health care-related BSI. Empirical therapy and targeted therapy were appropriate for 61% and 94% of cases, respectively. Increased 10-day mortality was associated with severe sepsis, septic shock, increasing age, and any focus other than the urinary tract. Decreased mortality was associated with receiving at least one active antibiotic within the first 48 hours. Intervention of antimicrobial management team during the acute phase of BSI was associated with a decreased mortality at day 10 in the overall population and in health care-related BSI. CONCLUSION: Optimizing BSI management by increasing rapidity of appropriate treatment initiation may decrease short-term mortality, even in countries with low rate of multidrug-resistant organisms. Early intervention of antimicrobial management team is crucial in terms of mortality.

Carbapenem use in French hospitals: A nationwide survey at the patient level.

The objective of this study was to evaluate the characteristics of carbapenem use in French healthcare settings in order to guide future actions. Healthcare facilities voluntarily participated in a nationwide cross-sectional survey in 2011. Medical data and reasons for carbapenem treatment (CPR) and discontinuation were recorded for all patients treated with carbapenems. A total of 2338 patients were recorded by 207 facilities. The median duration of CPR was 8 days, and 31.4% of patients received CPR for >10 days. An antibiotic consultant was involved in the initial choice of CPR in 36.8% of cases. CPR was chosen on an empirical (EP) basis for 1229 patients (52.6%), mainly because of severe sepsis (48.6%) or a perceived risk of bacterial resistance (33.7%). Among EP patients, de-escalation was more frequent in the case of intervention of an antibiotic consultant (35.1%) than without intervention (22.9%) (P<0.01). Among the 1109 patients receiving CPR initially based on bacteriological results, 607 (54.7%) had ESBL-producing Enterobacteriaceae and 397 (35.8%) had Gram-negative bacilli susceptible to at least one ß-lactam other than carbapenems or to fluoroquinolones. Among the latter, de-escalation was performed in 59 cases (14.9%). The intervention of an antibiotic consultant did not favour de-escalation in this group. In conclusion, carbapenems are frequently used for treating suspected or confirmed multidrug-resistant bacteria, and overall CPR duration is long. De-escalation is frequently not implemented despite isolates being susceptible to other drugs. More frequent antibiotic consultant intervention may help to decrease carbapenem use in the case of EP treatment.

Role of biomarkers in the management of antibiotic therapy: an expert panel review: I - currently available biomarkers for clinical use in acute infections.

In the context of worldwide increasing antimicrobial resistance, good antimicrobial prescribing in more needed than ever; unfortunately, information available to clinicians often are insufficient to rely on. Biomarkers might provide help for decision-making and improve antibiotic management. The purpose of this expert panel review was to examine currently available literature on the potential role of biomarkers to improve antimicrobial prescribing, by answering three questions: 1) Which are the biomarkers available for this purpose?; 2) What is their potential role in the initiation of antibiotic therapy?; and 3) What is their role in the decision to stop antibiotic therapy? To answer these questions, studies reviewed were limited to recent clinical studies (<15 years), involving a substantial number of patients (>50) and restricted to controlled trials and meta-analyses for answering questions 2 and 3. With regard to the first question concerning routinely available biomarkers, which might be useful for antibiotic management of acute infections, these are currently limited to C-reactive protein (CRP) and procalcitonin (PCT). Other promising biomarkers that may prove useful in the near future but need to undergo more extensive clinical testing include sTREM-1, suPAR, ProADM, and Presepsin. New approaches to biomarkers of infections include point-of-care testing and genomics.

Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy.

Biomarker-guided initiation of antibiotic therapy has been studied in four conditions: acute pancreatitis, lower respiratory tract infection (LRTI), meningitis, and sepsis in the ICU. In pancreatitis with suspected infected necrosis, initiating antibiotics best relies on fine-needle aspiration and demonstration of infected material. We suggest that PCT be measured to help predict infection; however, available data are insufficient to decide on initiating antibiotics based on PCT levels. In adult patients suspected of community-acquired LRTI, we suggest withholding antibiotic therapy when the serum PCT level is low (<0.25 ng/mL); in patients having nosocomial LRTI, data are insufficient to recommend initiating therapy based on a single PCT level or even repeated measurements. For children with suspected bacterial meningitis, we recommend using a decision rule as an aid to therapeutic decisions, such as the Bacterial Meningitis Score or the Meningitest®; a single PCT level ≥0.5 ng/mL also may be used, but false-negatives may occur. In adults with suspected bacterial meningitis, we suggest integrating serum PCT measurements in a clinical decision rule to help distinguish between viral and bacterial meningitis, using a 0.5 ng/mL threshold. For ICU patients suspected of community-acquired infection, we do not recommend using a threshold serum PCT value to help the decision to initiate antibiotic therapy; data are insufficient to recommend using PCT serum kinetics for the decision to initiate antibiotic therapy in patients suspected of ICU-acquired infection. In children, CRP can probably be used to help discontinue therapy, although the evidence is limited. In adults, antibiotic discontinuation can be based on an algorithm using repeated PCT measurements. In non-immunocompromised out- or in- patients treated for RTI, antibiotics can be discontinued if the PCT level at day 3 is < 0.25 ng/mL or has decreased by >80-90%, whether or not microbiological documentation has been obtained. For ICU patients who have nonbacteremic sepsis from a known site of infection, antibiotics can be stopped if the PCT level at day 3 is < 0.5 ng/mL or has decreased by >80% relative to the highest level recorded, irrespective of the severity of the infectious episode; in bacteremic patients, a minimal duration of therapy of 5 days is recommended.

Clinical and microbiological profiles of community-acquired and nosocomial intra-abdominal infections: results of the French prospective, observational EBIIA study.

OBJECTIVES: The EBIIA (Etude épidémiologique Bactério-clinique des Infections Intra-Abdominales) study was designed to describe the clinical, microbiological and resistance profiles of community-acquired and nosocomial intra-abdominal infections (IAIs). PATIENTS AND METHODS: From January to July 2005, patients undergoing surgery/interventional drainage for IAIs with a positive microbiological culture were included by 25 French centres. The primary endpoint was the epidemiology of the microorganisms and their resistance to antibiotics. Multivariate analysis was carried out using stepwise logistic regression to assess the factors predictive of death during hospitalization. RESULTS: Three hundred and thirty-one patients (234 community-acquired and 97 nosocomial) were included. The distribution of the microorganisms differed according to the type of infection. Carbapenems and amikacin were the most active agents in vitro against Enterobacteriaceae in both community-acquired and nosocomial infections. Against Pseudomonas aeruginosa, amikacin, imipenem, ceftazidime and ciprofloxacin were the most active agents in community-acquired infections, while imipenem, cefepime and amikacin were the most active in nosocomial cases. Against the Gram-positive bacteria, vancomycin and teicoplanin were the most active in both infections. Against anaerobic bacteria, the most active agents were metronidazole and carbapenems in both groups. Empirical antibiotic therapy adequately targeted the pathogens for 63% of community-acquired and 64% of nosocomial peritonitis. The presence of one or more co-morbidities [odds ratio (OR) = 3.17; P = 0.007], one or more severity criteria (OR = 4.90; P < 0.001) and generalized peritonitis (OR = 3.17; P = 0.006) were predictive of death. CONCLUSIONS: The principal results of EBIIA are a higher diversity of microorganisms isolated in nosocomial infections and decreased susceptibility among these strains. Despite this, the adequacy of treatment is comparable in the two groups.

Epidemiology, management, and prognosis of secondary non-postoperative peritonitis: a French prospective observational multicenter study.

BACKGROUND: Despite improvements in treatment, secondary peritonitis still is associated with high morbidity and mortality rates. Better knowledge of real-life clinical practice might improve management. METHODS: Prospective, observational study (January-June 2005) of 841 patients with non-postoperative secondary peritonitis. RESULTS: Peritonitis originated in the colon (32% of patients), appendix (31%), stomach/duodenum (18%), small bowel (13%), or biliary tract (6%). Most patients (78%) presented with generalized peritonitis and 26% with severe peritonitis (Simplified Acute Physiology Score [SAPS] II score>38). Among the 841 patients, 27.3% underwent laparoscopy alone; 11% underwent repeat surgery, percutaneous drainage, or both. A SAPS II score>38 and the presence of Enterococcus spp. were predictive of abdominal and non-surgical infections (odds ratio [OR]=1.84; p=0.013 and OR=2.93; p<0.0001, respectively). A SAPS II score>38 also was predictive of death (OR=10.5; p<0.0001). The overall mortality rate was high (15%). Patients receiving inappropriate initial antimicrobial therapy had significantly higher morbidity and mortality rates than patients receiving appropriate therapy (44 vs. 30%; p=0.004 and 23% vs. 14%; p=0.015, respectively). The SAPS II score and rates of severe peritonitis, morbidity, and mortality were significantly lower in patients with appendiceal peritonitis. CONCLUSIONS: Patients with non-postoperative peritonitis should be considered high risk and should receive appropriate initial therapy. The presence of Enterococcus spp. in peritoneal cultures significantly increased morbidity but not the mortality rate. Appendiceal peritonitis that was less severe and had a better prognosis than peritonitis originating in other sites should be considered a special case in future studies.