Proposal for shorter antibiotic therapies.

OBJECTIVES: Reducing antibiotic consumption has now become a major public health priority. Reducing treatment duration is one of the means to achieve this objective. Guidelines on the therapeutic management of the most frequent infections recommend ranges of treatment duration in the ratio of one to two. The Recommendation Group of the French Infectious Diseases Society (SPILF) was asked to collect literature data to then recommend the shortest treatment durations possible for various infections. METHODS: Analysis of the literature focused on guidelines published in French and English, supported by a systematic search on PubMed. Articles dating from one year before the guidelines publication to August 31, 2015 were searched on the website. RESULTS: The shortest treatment durations based on the relevant clinical data were suggested for upper and lower respiratory tract infections, central venous catheter-related and uncomplicated primary bacteremia, infective endocarditis, bacterial meningitis, intra-abdominal, urinary tract, upper reproductive tract, bone and joint, skin and soft tissue infections, and febrile neutropenia. Details of analyzed articles were shown in tables. CONCLUSION: This work stresses the need for new well-conducted studies evaluating treatment durations for some common infections. Following the above-mentioned work focusing on existing literature data, the Recommendation Group of the SPILF suggests specific study proposals.

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.

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.

[Bacteriological analysis of more than 600 febrile urinary infections managed in a community health network]. / Analyse microbiologique de plus de 600 infections urinaires fébriles prises en charge dans un réseau de soin.

UNLABELLED: Community-acquired febrile urinary tract infections (UTI) in adult has received little attention in the literature. The objective of our study was to determinate the distribution of bacterial strains isolated from adults with community-acquired febrile UTI and antibiotic susceptibility patterns of Escherichia coli. PATIENTS AND METHOD: We studied the SPHERES's databank. SPHERES is a Parisian medical community network aimed at securing and facilitating the ambulatory management of potentially serious acute illnesses. Each patient is included in the network according to specific clinical criteria and standardized medical data are recorded. We retrospectively studied the medical records of all patients treated for a pyelonephritis or a prostatitis between April 2005 and October 2008. RESULTS: Five hundred and sixty-eight patients were enrolled: 410 women and 158 men. The overall bacteria's distribution was similar to that observed in previous strictly microbiological studies with a more prominent role of E. coli (87.5%) to the detriment of other species. The overall susceptibility of E. coli to antibiotics recommended in the empiric treatment of pyelonephritis and prostatitis was preserved: ciprofloxacin (95.8%), cefotaxime (98%), gentamicin (99.4%). In women over 65 years, the susceptibility of E. coli to systemic fluoroquinolones fell up 89.7%. This could affect the empiric oral treatment of pyelonephritis in older women. CONCLUSIONS: We report the bacterial distribution and the resistance pattern of bacteria implicated in febrile urinary infections diagnosed and treated in a health network. It seems that E. coli resistance increased more in women more than 65 years than in men.

Point prevalence survey of antibiotic use in French hospitals in 2009.

OBJECTIVES: To evaluate the feasibility of a point prevalence survey for monitoring antibiotic use in a voluntary sample of French hospitals. METHODS: Demographic and medical data were collected for all inpatients. Additional characteristics regarding antimicrobial treatment, type of infection and microbiological results were collected only for patients receiving antimicrobials. RESULTS: Among 3964 patients in 38 hospitals, 343 (8.7%) received antimicrobial prophylaxis and 1276 (32.2%) antimicrobial therapy. The duration of surgical antimicrobial prophylaxis was >1 day in 41 out of 200 (21%) of the cases. Among patients with antimicrobial therapy, 959 (75.2%) received ß-lactams (including 34.8% penicillins with ß-lactam inhibitors, 22.1% third-generation cephalosporins and 7.8% carbapenems) and 301 (23.6%) received fluoroquinolones (50% orally). A total of 518 (40.6%) patients were treated with more than one drug and 345 (27.2%) were treated for >7 days. Patients treated for hospital-acquired infections (39.2%) were more likely to receive combinations (47.6% versus 34.4%, P < 0.01), carbapenems (14.4% versus 2.6%, P < 0.01), glycopeptides (14.4% versus 3.7%, P < 0.01) and antifungals (17% versus 5.3%, P < 0.01) for a longer duration (7.8 versus 6 days, P < 0.01). Fifty-six patients (4.4%) were treated for >7 days and did not have any microbiological sample drawn. The time allocated for the survey represented 18.3-25.0 h for 100 patients. CONCLUSIONS: The data provide directions for further interventions, such as better use of diagnostic tools, decreasing the treatment duration and the use of combinations. In addition, the survey shows that, although cumbersome, it is feasible to improve the representativeness of national data in European surveys.

[Community- and non-community-acquired bacteremia: correlation between empiric antimicrobial therapy and susceptibility of micro-organisms isolated during 2007 in the Ile-de-France microbiologists network]. / Anti-infectieux empiriques dans les 24-48 premières heures des bactériémies des patients hospitalisés dans les hôpitaux du groupe des microbiologistes d'Ile-de-France en 2007.

AIM OF THE STUDY: To estimate the percentage of empirical treatments adapted in the bloodstream infections of community and not community origin and to determine the main circumstances in which this initial treatment is not adapted. PATIENTS AND METHODS: Surveillance of bloodstream infections from the laboratories of microbiology of the eight hospitals of the Ile-de-France network, during year 2007. The study concerned the patients hospitalised in medicine, surgery, obstetrics, intensive care, following care and rehabilitation, day hospitalisation, hospitalisation at home, who presented one or several episodes of bloodstream infections. RESULTS: During year 2007, 2013 bloodstream infections were analysed. Only 63.9% of bloodstream infections had an adapted initial antibiotic treatment. Among this proportion of bloodstream infections, an adapted empirical treatment concerned mainly the community episodes, the urinary tract, the pulmonary tract, or maternal-foetal episodes and the maternity ward and pediatrics. The percentage of adapted treatments was superior in the bloodstream infections where were isolated an Enterobacteriaceae, Streptococcus pneumoniae or other streptococci. On the contrary, only a quarter of bloodstream infections due to an Enterobacteriaceae producing BLSE or to a MRSA had received an adapted empirical treatment. CONCLUSION: Only two-thirds of the patients developing a bloodstream infection received an adapted initial antibiotic treatment. This proportion was even lower when it was not about a community origin, in spite of the frequent administration of several anti-infectious molecules or with wide spectrum.

[Pleural diffusion of amoxicillin 1 and vancomycin in patients treated for post-surgical empyema]. / Empyème après chirurgie d'exérèse pulmonaire: étude de la diffusion pleurale de l'amoxicilline et de la vancomycine.

INTRODUCTION: Treatment of post surgical thoracic empyema consists of chest tube drainage, antibiotic administration, and in some cases surgical lavage of infected spaces. Data in human on the diffusion of antibiotics in pleural cavity after post surgical empyema are lacking. METHODS: We studied on 9 patients with post surgical thoracic empyema (including 6 pneumonectomy) the diffusion of 2 antibiotics commonly used in this situation: amoxicillin (for 7 patients) and vancomycin (for 2 patients). Antibiotics concentrations were measured after at least 3 days of treatment (3-12 days), in order to reach a plateau concentration in the pleural space. RESULTS: The ratio pleural/plasma antibiotic concentration was 1.96 (range: 0.6-4.9). The pleural infection was cured for 8 on 9 patients. The last patients required thoracostomy, and the outcome was favorable after this procedure. CONCLUSION: That the penetration of amoxicillin and vancomycin in pleural space after post surgical empyema is good. Pleural antibiotics concentrations are in the majority of cases higher than plasmatic concentrations.

[Current management of acute pediatric rhinosinusitis in France]. / Etat actuel de la prise en charge des infections rhinosinusiennes aiguës de l'enfant en France.

A multidisciplinary panel of specialists and general practitioners provided definitions for the different forms of acute pediatric rhinosinusitis, with a description of the main symptoms and signs. They emphasized the role of concomitant systemic diseases, such as allergy and immunological disorders. Incidence, description, and management of complications are presented. They also provided the indications for radiological examination and microbiological investigations. The adequate medical management, particularly the place and the type of antibiotics, is analyzed and discussed, and guidelines for practical situations are suggested.

[Evolution of susceptibility of aerobic gram-negative aerobic bacilli to quinolones and fluoroquinolones in a university hospital (1992-2000)]. / Evolution de la sensibilité aux quinolones et aux fluoroquinolones des bacilles à Gram négatif aérobies isolés dans un hôpital universitaire (1992-2000).

Susceptibility to quinolones of aerobic gram-negative bacilli was assessed in a 2000-bed university hospital from 1992 to 2000. There was a significant downward trend in the rate of susceptibility to nalidixic acid (Nal) for Enterobacteriaceae as a whole from 1992 to 2000 (86% vs 82%), and E. coli (92% vs 84%), and an upward trend for K. pneumoniae (74% vs 82%), the latter being related to the control of the spread of epidemic ESBL producing strains. The overall susceptibility of Enterobacteriaceae to ciprofloxacin (Cip) paralleled the susceptibility to Nal: decreased susceptibility for Enterobacteriaceae as a whole (96% vs 89%) and E. coli (99% vs 91%). A clear decrease in the level of susceptibility to Cip occurred during the study period among the Nal-resistant strains as demonstrated by the decrease in the median zone diameter (D) observed among the Nal-resistant strains of E. coli (26 mm in 1992 vs 19 mm in 1998-2000). The zone diameter distribution pattern changed from an unimodal distribution in 1992 to a trimodal distribution in 2000 secondary to the occurrence of a population of resistant strains (D = 13 mm) and of a highly resistant population (D = 6 mm). Finally, the susceptibility to Cip of P. aeruginosa strains remained stable around 62% throughout the study period.

Trends in quinolone susceptibility of Enterobacteriaceae among inpatients of a large university hospital: 1992-98.

OBJECTIVES: To assess trends in quinolone susceptibility of Enterobacteriaceae isolated in a large university hospital. METHODS: Between 1992 and 1998, bacterial isolates were collected each year during a 3-month period to evaluate annual changes in susceptibility. In addition, the activities of fluoroquinolones (pefloxacin, norfloxacin, ofloxacin, ciprofloxacin) against nalidixic acid-resistant strains were determined by disk diffusion and MIC methodologies during the first and last year of the study. RESULTS: The susceptibility of Enterobacteriaceae to nalidixic acid was unchanged between 1992 and 1998 (86% versus 85%). However, at the species level, the susceptibility rates to nalidixic acid decreased for Escherichia coli from 92% to 89%, and for Enterobacter cloacae from 87% to 82%. In contrast, there was a 10% increase in the nalidixic acid susceptibility rates for Klebsiella pneumoniae (74% versus 83%), which was thought to be due to the control of the spread of epidemic extended-spectrum beta-lactamase (ESBL)-producing strains. The overall susceptibility of the Enterobacteriaceae to the fluoroquinolones remained high during the study period, greater than 90% in the case of ciprofloxacin. However, nalidixic acid-resistant Escherichia coli showed decreased susceptibility to ciprofloxacin between 1992 and 1998, as reflected by a decrease in median zone diameter (26 mm to 19 mm), an increase in MIC(50) (0.25 mg/L to 1 mg/L) and a shift in MIC distribution (unimodal in 1992 to bimodal in 1998). This has resulted in the reduced susceptibility of Escherichia coli to fluoroquinolones between 1992 and 1998 (pefloxacin, 95-90%; ciprofloxacin, 99-95%). CONCLUSIONS: The susceptibility of Escherichia coli to quinolones has decreased, and the level of susceptibility of the resistant strains has increased over the 7-year study period.

Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study.

A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC(24h)) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg(2)/liter(2)/h(2) [P = 0.026] and 414 versus 818 g(2) [P = 0.057], respectively). The 10-day treatment cost per patient was $454 +/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/- 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.

[Surveillance of bacterial antibiotic resistance]. / Surveillance de la résistance bactérienne aux antibiotiques.

A NEW RESISTANCE MECHANISM FOR E. COLI: E. coli can develop plasmid-transmitted resistance against fluoroquinolones via a specific protection of DNA gyrase. FOR STREPTOCOCCI: Two mechanisms of natural or acquired resistance linked to 2 genes can be considered: ermTR/B leads to the synthesis of methylase, the most frequent mechanism; mef E/A causes active efflux. For S. pyogenes, resistance against macrolides varies from one country to another; it is 9.6% in France. Among the commensal flora of the oropharynx, S. viridans, is the most important reservoir of resistance against macrolides. ANIMAL RESERVOIRS: Both house pets and farm animals constitute a reservoir of resistant bacteria. It is difficult to establish a relationship between the use of antibiotics and the frequency of resistance. The presence of a relationship between animal reservoirs and human infection remains controversial. ANTIBIOTIC USE AND RESISTANCE: Several publications have concluded that, from an individual point of view, there is a quasi-direct relationship between antibiotic use and bacterial resistance to antibiotics. Actually, the methodology of most of these studies can be criticized because they did not follow 3 fundamental rules: selection of controls, date the risk was measured, comorbidity.

[Phare study. Comparative study of combined cefepime-amikacin versus ceftazidime combined with amikacin in the treatment of nosocomial pneumonias in ventilated patients. Multicenter group study]. / Etude phare. Etude comparative de l'association céfépime-amikacine versus ceftazidime en association avec l'amikacine dans le traitement des pneumonies nosocomiales chez les patients ventilés. Le groupe multicentrique de l'étude.

OBJECTIVE: To compare the associations of cefepime (2 g x 2/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefe-ami) and ceftazidime (2 g x 3/day) + amikacin (7.5 mg.kg-1 x 2/day) (= cefta-ami) in patients under mechanical ventilation suffering from a nosocomial pneumonia. STUDY DESIGN: Multi-centre, open, comparative, randomised study. PATIENTS: The study included 275 ICU patients enrolled either in the cefe-ami group (n = 141) or in the cefta-ami group (n = 134). METHODS: All cases were reviewed in a blinded fashion by the steering committee. RESULTS: Microbiology laboratory tests were positive in 74% of patients of the cefe-ami group and in 63% of the cefta-ami group respectively; 319 presumed causative strains of bacteria were isolated. The mean duration of treatment was 12 days for cefepime, 11 days for ceftazidime and 8 days for amikacin. In intention to treat, the clinical recovery rate was 48.2% in the cefe-ami group and 44.8% in the cefta-ami group respectively. In the population with a documented pneumonia, the clinical recovery was significantly better in the cefe-ami group (53.3%), than in the cefta-ami group (39.3%) (P = 0.05). In per protocol analysis, these rates reached 67.7% in the cefe-ami group and 68.2% in the cefta-ami group respectively. In the bacteriologically documented cases the eradication rates were 86.5% and 89.3% respectively. CONCLUSION: The efficacy rates of cefe-ami and cefta-ami combinations were similar in ICU patients under mechanical ventilation with a nosocomial pneumonia. However the cefe-ami association was significantly more efficient in the population with a bacteriologically documented pneumonia.

Highlights of the French Antimicrobial Resistance Surveillance Project. French Study Group.

Thirty-three French laboratories took part in a study to determine the frequency of antibiotic resistance to S. pneumoniae, H. influenzae and M. catarrhalis in different regions of the country. A total of 1317 bacterial isolates were studied. The level of resistance to penicillin among isolates of S. pneumoniae was high particularly in children with otitis media or upper respiratory tract infections. In H. influenzae isolates the level of beta-lactamase production was over 30% in all groups of patients and specimen types and in M. catarrhalis the level of beta-lactamase production was in excess of 90%. Multidrug resistance was found often among the macrolides, tetracyclines, and trimethoprim/sulfamethoxazole, and these antimicrobials should not be regarded as therapeutic alternatives to the beta-lactams.

Resistance to ceftriaxone and other beta-lactams in bacteria isolated in the community. The Vigil'Roc Study Group.

The incidence of bacterial species and their susceptibilities to ceftriaxone and other beta-lactams from patients with community-acquired infections were evaluated in a multicenter study over a 4-month period. A total of 5,768 bacterial isolates were classified according to whether the patient had been previously hospitalized or had received antibiotic treatment. The most relevant findings were the presence of 33.8% penicillin-resistant Streptococcus pneumoniae isolates, 25% beta-lactamase-producing Haemophilus influenzae isolates, and 36.4% amoxicillin-resistant Escherichia coli isolates. All of these bacteria were fully susceptible to ceftriaxone. Nosocomial multiply-resistant bacteria, and particularly methicillin-resistant S. aureus, were found, as expected, at a higher frequency among previously hospitalized patients. However, such bacteria may be present in the community; their incidence is high in particular clinical settings, and such bacteria should be considered when one is choosing a first-line therapy for the treatment of severe infections.

[Retrospective study of the prevalence and sensitivity to antibiotics of bacteria isolated from ocular samplings]. / Etude rétrospective de la prévalence et de la sensibilité aux antibiotiques des bactéries isolées de prélèvements oculaires.

PURPOSE: This study evaluates the variability of the bacterial flora and the changes in their antibiotics sensitivity tests between 1988 and 1993 in 46090 specimens (conjunctival cultures, corneal scrapings, vitreous, aqueous humour, ocular foreign bodies). METHODS: The specimens were cultured and antibiotics sensitivity test was carried out on the pathogens only (3309 strains). RESULTS: Streptococci (36.1%) and Staphylococcus aureus (35.6%) are the most frequent species with Enterobacteriaceae (12.1%) and Haemophilus (7.8%). S. aureus and Streptococcus pneumoniae are more prevalent with decreasing values for other bacteria (Khi-2 of trend, Mantel's extension, p < 0.05). Antibiotics sensitivity yield expected results without any remarkable changes during the study. No multi-resistant strain was isolated. CONCLUSION: The increase of number of S. aureus and S. pneumoniae is the major change noted in pathogens found from our eye samples.

Use of cefotaxime or ceftazidime susceptibility tests for predicting susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa.

To determine if susceptibility to aztreonam could be predicted from cefotaxime or ceftazidime disc diffusion testing, 919 Enterobacteriaceae and 187 Pseudomonas aeruginosa clinical strains were studied. The correlation coefficient between the diameters of inhibition zones was 0.9 for cefotaxime versus aztreonam and ceftazidime versus aztreonam comparisons in Enterobacteriaceae and 0.75 for ceftazidime versus aztreonam comparison in P. aeruginosa. For 99% of the Enterobacteriaceae, there was no risk in predicting susceptibility to aztreonam on the basis of cefotaxime or ceftazidime susceptibility tests. To minimize the risk of the remaining 1% of the strains being erroneously classified as susceptible to aztreonam, ceftoaxime should be tested in preference to ceftazidime, and the production of extended-spectrum beta-lactamases should be tested for using the cefotaxime-clavulanate disc synergy test. For P. aeruginosa strains, susceptibility to aztreonam could be accurately predicted from ceftazidime susceptibility tests for ticarcillin susceptible strains, but for ticarcillin resistant strains, susceptibility to aztreonam should be tested.