Claire Bernède-Bauduin

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007

Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children.

Major Role for Amphotericin B–Flucytosine Combination in Severe Cryptococcosis

Background The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. Methodology/Principal Findings Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21–16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23–12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32–12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10–6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12–9.70], p = 0.030) were independently associated with treatment failure at Mo3. Conclusion/Significance Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis.

Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations

BACKGROUND Clinical observations suggest that Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) may affect cystic fibrosis (CF) patients with different characteristics and risk factors, but this has never been demonstrated within a single prospective cohort. METHODS We studied 50 MABSC-positive and 23 MAC-positive patients from a French prevalence study of non-tuberculous mycobacteria (NTM) in CF. Risk factors specifically associated with MABSC and MAC were analyzed by nested case-control studies, with two NTM-negative controls matched by age, sex and center for each case. RESULTS MAC-positive patients were significantly older than MABSC-positive patients (mean [SD] age, 23.1 [10.2] vs 17.4 [8.3] years, p=0.013), and were also older at CF diagnosis (mean [SD] age, 12.9 [16.1] vs 3.1 [7.7] years, p=0.015); they tended to be less frequent of the ΔF508/ΔF508 genotype (33.3 vs 61.1%, p=0.17) and to use pancreatic extracts less frequently (82.4 vs 97.6%, p=0.07). Risk factors identified by multivariate analysis were: i) in the MAC case-control study, an older age at CF diagnosis (p=0.004); ii) in the MABSC case-control study, at least one course of intravenous antibiotics (p=0.01) and more frequent isolation of Aspergillus (p=0.03). CONCLUSIONS MAC affects adult patients with a mild form of CF, whereas MABSC affects younger patients with more severe CF and more frequent intravenous antimicrobial treatment.

Is exposure to mercury a driving force for the carriage of antibiotic resistance genes

The mercury resistance gene merA has often been found together with antibiotic resistance genes in human commensal Escherichia coli. To study this further, we analysed mercury resistance in collections of strains from various populations with different levels of mercury exposure and various levels of antibiotic resistance. The first population lived in France and had no known mercury exposure. The second lived in French Guyana and included a group of Wayampi Amerindians with a known high exposure to mercury. Carriage rates of mercury resistance were assessed by measuring the MIC and by detecting the merA gene. Mercury-resistant E. coli was found significantly more frequently in the populations that had the highest carriage rates of antibiotic-resistant E. coli and in parallel antibiotic resistance was higher in the population living in an environment with a high exposure to mercury, suggesting a possible co-selection. Exposure to mercury might be a specific driving force for the acquisition and maintenance of mobile antibiotic resistance gene carriage in the absence of antibiotic selective pressure.

Characteristics of human intestinal Escherichia coli with changing environments.

To investigate if the characteristics of human intestinal Escherichia coli are changing with the environment of the host, we studied intestinal E. coli from subjects having recently migrated from a temperate to a tropical area. We determined the phylogenetic group, the prevalence of the antibiotic resistance, the presence of integrons and the strain diversity in faecal isolates from 25 subjects originally from metropolitan France and expatriated to French Guyana. These characteristics were compared with those of 25 previously studied Wayampi Amerindian natives of French Guyana and from 25 metropolitan French residents. The three groups of subjects were matched for age and sex, had not taken antibiotics for at least 1 month, nor had been hospitalized within the past year. In all, the characteristics of intestinal E. coli from Expatriates were intermediate between those found in residents from metropolitan France and those found in natives of French Guyana. Prevalence of carriage of resistant Gram-negative bacteria in Expatriates was intermediate between French residents and Wayampi as were the prevalence of integrons in E. coli (12.3% versus 16.3% and 7.8% respectively), and the intra-host diversity of E. coli (2.3 strains/subject versus 1.9 and 3.1, respectively); lastly, in Expatriates, the prevalence of carriage of phylogenetic group B2 strains was lower than in French residents (16% versus 56%, P = 0.005), while carriage of phylogenetic group A strains was lower than in Wayampi (56% versus 88%, P = 0.03). Our results suggest that the composition of the commensal intestinal flora of humans is not static but changes dynamically in response to new environmental conditions.

Variability of intestinal colonization with third-generation cephalosporin-resistant Enterobacteriaceae and antibiotic use in intensive care units

OBJECTIVES Healthcare-associated infections due to third-generation cephalosporin-resistant Enterobacteriaceae (CRE) have become a major public health threat, especially in intensive care units (ICUs). We assessed and compared β-lactam use, the prevalence of colonization with CRE at admission and the incidence of CRE acquisition across ICUs. PATIENTS AND METHODS A cohort study was conducted in 10 ICUs of the Paris (France) metropolitan area between November 2005 and February 2006. Antibiotic use was recorded prospectively in all patients admitted during the study period. Rectal swabs were collected at admission, twice weekly thereafter, before β-lactam prescription and before discharge. RESULTS A total of 893 patients provided 3453 rectal swabs; 793 of the patients were newly admitted, mostly for medical reasons (80.7%). On admission, 74 patients (9.6%) were colonized with CRE, including 32 with an extended-spectrum β-lactamase (ESBL)-producing strain. Among the remaining 694 naive patients, 94 acquired CRE during their follow-up, including 31 with an ESBL-producing strain. Incidence rates of colonization ranged from 8.8 to 21.0/1000 patient-days for all CRE, and from 1.4 to 10.9/1000 patient-days for ESBL producers. A majority of patients (68.3%) were prescribed β-lactams during their ICU stay, with defined daily doses ranging from 428 to 985/1000 patient-days. Across ICUs, prescriptions of all antibiotics, β-lactams and carbapenems were significantly correlated to incidence rates of colonization with ESBL-producing CRE. CONCLUSIONS The standardized and systematic follow-up of patients in 10 ICUs revealed great heterogeneity in the rates of colonization with ESBL- and non-ESBL-producing CRE, as well as in antimicrobial prescription practices.

Inhaled therapies, azithromycin and Mycobacterium abscessus in cystic fibrosis patients

Cystic fibrosis (CF) patients are at particularly high risk of developing lung disease caused by Mycobacterium abscessus complex (MABSC). Over the last 10 years, changes in CF treatment, with increasing use of inhaled therapies and low-dose azithromycin, have been accompanied by an increase in the prevalence of MABSC infections in CF patients. There is therefore some concern about the role of new CF treatments in the emergence of MABSC infections. We addressed this issue by means of a case–control study including 30 MABSC-positive cases and 60 nontuberculous mycobacteria-negative CF controls matched for age, sex and centre. We also compared practices at the CF centres with the highest prevalence of MABSC with those at the other centres. No positive association was found between MABSC lung disease and the use of inhaled therapies or low-dose azithromycin in the 4 years preceding MABSC isolation. These treatments were not significantly more frequently used at the CF centres with the highest MABSC prevalence rates. In conclusion, there is no evidence for a link between M. abscessus complex lung disease and inhaled therapies or low-dose azithromycin in patients with CF.

Diagnostic Criteria of Urinary Tract Infection in Male Patients With Spinal Cord Injury

Background. The current diagnostic criteria of urinary tract infection (UTI) in male patients with spinal cord injury (SCI) are not clear. Methods. The authors studied 381 episodes of “symptomatic” UTI (209 participants) and 277 episodes of “asymptomatic” UTI (205 participants) in male SCI patients using intermittent catheterization. UTI was defined as a bacterial count ≥102 colony-forming units (cfu)/mL (American Paraplegia Society criterion). Univariate analysis and receiver operating characteristic (ROC) curve analysis were used to determine optimal cfu and white blood cell (WBC) thresholds. Results. The most prevalent clinical signs, alone or in combination, were cloudy and/or malodorous urine (51.4%), onset of urinary incontinence (51.2%), fatigue (41.7%), fever (30.7%), and increased spasticity (30.2%). Urine cfu and WBC levels in patients with only one sign, including fever, were not significantly higher than those in asymptomatic controls. WBC, but not cfu, levels increased significantly with the number of signs (P = .026). Univariate analysis and ROC curve analysis failed to identify cfu, WBC, or a combination of cfu and WBC count thresholds, allowing discrimination between the symptomatic and asymptomatic UTI groups. Conclusions. Clinical signs of UTI correlate poorly with the urine cfu and WBC levels in SCI patients, except for a positive relationship between WBC counts and the number of signs. Fever alone has no higher diagnostic value. There are no satisfactory cfu and WBC thresholds: thresholds more restrictive than the current American Paraplegia Society criteria provide higher specificity values but with equivalent loss of sensitivity.