Time to intestinal clearance of carbapenemase-producing Enterobacterales in hospital patients: a longitudinal retrospective observational cohort study.

BACKGROUND: Intestinal clearance of carbapenemase-producing Enterobacterales (CPE-IC) is a cornerstone to discontinue isolation precautions for CPE patients in hospitals. This study aimed to evaluate the time to spontaneous CPE-IC and identify its potential associated risk factors. METHODS: This retrospective cohort study was carried out between January 2018 and September 2020 on all patients in a 3200-bed teaching referral hospital with confirmed CPE intestinal carriage. CPE-IC was defined as at least three consecutive CPE-negative rectal swab cultures without a subsequent positive result. A survival analysis was performed to determine the median time to CPE-IC. A multivariate Cox model was implemented to explore the factors associated with CPE-IC. RESULTS: A total of 110 patients were positives for CPE, of whom 27 (24.5%) achieved CPE-IC. Median time to CPE-IC was 698 days. Univariate analysis showed that female sex (P=0.046), multiple CPE-species in index cultures (P=0.005), Escherichia coli or Klebsiella spp. (P=0.001 and P=0.028, respectively) were significantly associated with the time to CPE-IC. Multivariate analysis highlighted that identification of E. coli carbapenemase-producing or CPEs harbouring ESBL genes in index culture extended the median time to CPE-IC, respectively (adjusted hazard ratio (aHR) = 0.13 (95% confidence interval: 0.04-0.45]; P=0.001 and aHR = 0.34 (95% confidence interval: 0.12-0.90); P=0.031). CONCLUSION: Intestinal decolonization of CPE can take several months to years to occur. Carbapenemase-producing E. coli are likely to play a key role in delaying intestinal decolonization, probably through horizontal gene transfer between species. Therefore, discontinuation of isolation precautions in CPE-patients should be considered with caution.

The impact of lymph node density as a predictive factor for survival and recurrence of tongue squamous cell carcinoma.

The oral tongue is considered the most frequently involved site in cases of oral squamous cell carcinoma (OSCC). Lymph node (LN) density, defined as the number of positive LNs divided by the total number of resected LNs, is considered an important prognostic factor in OSCC; however the cut-off point remains uncertain. A retrospective study was performed involving 104 patients who underwent a glossectomy procedure for oral tongue squamous cell carcinoma (OTSCC) between the years 2008 and 2018. LN density and other related prognostic factors, including pathological N-stage (pN), extranodal extension (ENE), perineural invasion (PNI), and depth of invasion (DOI), were investigated in relation to survival and recurrence rates. pN + stage, the presence of ENE, the presence of PNI, and increased DOI were found to be associated with increased LN density values, as well as lower patient survival and higher recurrence rates. The statistical analysis identified a cut-off point for LN density of 2.5%. In advanced stage disease, LN density values above 2.5% had a significant impact on the survival rate (P = 0.005), as well as the recurrence rate (P = 0.038). In conclusion, in addition to other previously known prognostic factors, LN density may serve as a strong prognostic factor for survival and recurrence in patients with advanced- and early-stage OTSCC.

Spontaneous decolonization during hospitalization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales.

This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads.

Association of transcription factor 7-like 2 gene (TCF7L2) polymorphisms with stress-related hyperglycaemia (SRH) in intensive care and resulting outcomes: The READIAB study.

OBJECTIVE: The study aimed to evaluate the impact of the single nucleotide polymorphism (SNP) rs7903146 on the transcription factor 7-like 2 (TCF7L2) gene in stress-related hyperglycaemia (SRH), defined as blood glucose≥11mmol/L in at least two blood samples during the first 3 days in the intensive care unit (ICU), and on 28-day and 1-year mortality, and incidence of type 2 diabetes (T2D) at 6 months and 1 year in patients hospitalized in the ICU. METHODS: This prospective observational (non-interventional) multicentre READIAB study, carried out during 2012-2016 in six French ICUs, involved adult patients admitted to ICUs for at least two organ failures; patients admitted for<48h were excluded. During the 3-day ICU observational period, genetic testing, blood glucose values and insulin treatment were recorded. MAIN RESULTS: The association of rs7903146 with SRH was assessed using logistic regression models. Cox proportional hazards regression models assessed the associations between rs7903146 and mortality and between SRH and mortality, both at 28 days and 1 year. A total of 991 of the 1000 enrolled patients were included in the READIAB-G4 cohort, but 242 (24.4%) had preexisting diabetes and were excluded from the analyses. SRH occurred within the first 3 days in the ICU for one-third of the non-diabetes patients. The association between the rs7903146 polymorphism and SRH did not reach significance (P=0.078): OR(peroneTcopy): 1.24, 95% CI: 0.98-1.58. A significant association was found between rs7903146 and 28-day mortality after adjusting for severity scores (P=0.026), but was no longer significant at 1 year (P=0.61). At 28 days, mortality was increased in patients with SRH (HR: 2.09, 95% CI: 1.43-3.06; P<0.001), and remained significant at 1 year after adjusting for severity scores (HR: 1.73, 95% CI: 1.32-2.28; P<0.001). On admission, non-diabetes patients with SRH had a higher incidence of T2D at 6 months vs. those without SRH (16.0% vs. 7.6%, RR: 2.11, 95% CI: 1.07-4.20; P=0.030). At 1 year, these figures were 13.4% vs. 9.2%, RR: 1.45, 95% CI: 0.71-2.96; P=0.31). Moreover, the rs7903146 polymorphism was not significantly associated with T2D development at either 6 months (P=0.72) or 1 year (P=0.64). CONCLUSION: This study failed to demonstrate any significant association between rs7903146 and SRH. Nevertheless, the issue remains an important challenge, as SRH may be associated with increased rates of both mortality and T2D development.

Towards precision medicine in sepsis: a position paper from the European Society of Clinical Microbiology and Infectious Diseases.

BACKGROUND: Our current understanding of the pathophysiology and management of sepsis is associated with a lack of progress in clinical trials, which partly reflects insufficient appreciation of the heterogeneity of this syndrome. Consequently, more patient-specific approaches to treatment should be explored. AIMS: To summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice. A secondary objective is to develop a framework enclosing recommendations on management and priorities for further research. SOURCES: A global search strategy was performed in the MEDLINE database through the PubMed search engine (last search December 2017). No restrictions of study design, time, or language were imposed. CONTENT: The focus of this Position Paper is on the interplay between therapies, pathogens, and the host. Regarding the pathogen, microbiologic diagnostic approaches (such as blood cultures (BCs) and rapid diagnostic tests (RDTs)) are discussed, as well as targeted antibiotic treatment. Other topics include the disruption of host immune system and the use of biomarkers in sepsis management, patient stratification, and future clinical trial design. Lastly, personalized antibiotic treatment and stewardship are addressed (Fig. 1). IMPLICATIONS: A road map provides recommendations and future perspectives. RDTs and identifying drug-response phenotypes are clear challenges. The next step will be the implementation of precision medicine to sepsis management, based on theranostic methodology. This highly individualized approach will be essential for the design of novel clinical trials and improvement of care pathways.

Emergence of Aspergillus fumigatus azole resistance in azole-naïve patients with chronic obstructive pulmonary disease and their homes.

Azole-resistant Aspergillus fumigatus (ARAF) has been reported in patients with chronic obstructive pulmonary disease (COPD) but has not been specifically assessed so far. Here, we evaluated ARAF prevalence in azole-naïve COPD patients and their homes, and assessed whether CYP51A mutations were similar in clinical and environmental reservoirs. Sixty respiratory samples from 41 COPD patients with acute exacerbation and environmental samples from 36 of these patient's homes were prospectively collected. A. fumigatus was detected in respiratory samples from 11 of 41 patients (27%) and in 15 of 36 domiciles (42%). Cyp51A sequencing and selection on itraconazole medium of clinical (n = 68) and environmental (n = 48) isolates yielded ARAF detection in 1 of 11 A. fumigatus colonized patients with COPD (9%) and 2 of 15 A. fumigatus-positive patient's homes (13%). The clinical isolate had no CYP51A mutation. Two environmental isolates from two patients harbored TR34 /L98H mutation, and one had an H285Y mutation. Coexistence of different cyp51A genotypes and/or azole resistance profiles was detected in 3 of 8 respiratory and 2 of 10 environmental samples with more than one isolate, confirming the need for a systematic screening of all clinically relevant isolates. The high prevalence of ARAF in patients with COPD and their homes supports the need for further studies to assess the prevalence of azole resistance in patients with Aspergillus diseases in Northern France.

Colonization pressure as a risk factor of ICU-acquired multidrug resistant bacteria: a prospective observational study.

The primary objective of this study was to evaluate the impact of colonization pressure on intensive care unit (ICU)-acquired multidrug resistant bacteria (MDRB). All patients hospitalized for more than 48 h in the ICU were included in this prospective observational study. MDRB were defined as methicillin resistant Staphylococcus aureus, Pseudomonas aeruginosa resistant to ceftazidime or imipenem, Gram-negative bacilli producing extended-spectrum beta-lactamases (ESBL), and all strains of Acinetobacter baumannii and Stenotrophomonas maltophilia. Colonization pressure was daily calculated in the three participating ICUs. Univariate and multivariate analyses were used to determine risk factors for ICU-acquired MDRB. Two hundreds and four (34%) of the 593 included patients acquired an MDRB during their ICU stay. Multivariate analysis identified colonization pressure as an independent risk factor for ICU-acquired MDRB (OR (95% CI) 4.18 (1.03-17.01), p = 0.046). Other independent risk factors for ICU-acquired MDRB were mechanical ventilation (3.08 (1.28-7.38), p = 0.012), and arterial catheter use (OR, 3.04 (1.38-6.68), p = 0.006). ICU-acquired MDRB were associated with increased mortality, duration of mechanical ventilation, and ICU stay. However, ICU-acquired MDRB was not independently associated with ICU-mortality. Colonization pressure is an independent risk factor for acquiring MDRB in the ICU.

Impact of a targeted isolation strategy at intensive-care-unit-admission on intensive-care-unit-acquired infection related to multidrug-resistant bacteria: a prospective uncontrolled before-after study.

Isolation of patients with multidrug resistant (MDR) bacteria is recommended to reduce cross-transmission of these bacteria. However, isolation of critically ill patients has several negative side effects. Therefore, we hypothesized that a targeted isolation strategy, based on the presence of at least one risk factor for MDR bacteria, would be not inferior to a systematic isolation strategy at intensive-care unit (ICU) admission. This prospective before-after study was conducted in a mixed ICU, during two 12-month periods, separated by a 1-month 'wash-out' period. During the before period, isolation was systematically performed in all patients at admission. During the after period, isolation was only performed in patients with at least one risk factor for MDR bacteria at admission. During the two periods, routine screening for MDR bacteria was performed at ICU admission, and isolation prescription was modified after receipt of screening result. Primary outcome was the percentage of patients with ICU-acquired infection (ICUAI) related to MDR bacteria, measured from ICU admission until ICU discharge or day 28, whatever happens first. A total of 1221 patients were included. No significant difference was found in ICUAI related to MDR bacteria (85 of 585 (14.5%) vs. 84 of 636 (13.2%) patients, risk difference, -1.3%, 95% confidence interval [-5.2 to 2.6%]) between the two periods, confirming the non-inferiority hypothesis. Our results suggest that targeted isolation of patients at ICU admission is not inferior to systematic isolation, regarding the percentage of patients with ICUAI related to MDR bacteria. Further randomized controlled multicentre studies are needed to confirm our results.

Accuracy of leptin serum level in diagnosing ventilator-associated pneumonia: a case-control study.

BACKGROUND: Undernutrition causes a reduction of body-fat mass and a decrease in the circulating concentration of leptin which impairs the production of proinflammatory cytokines and increases the incidence of infectious diseases. The main objective of this study was to determine whether leptin deficiency is a risk factor for ventilator-associated pneumonia (VAP). METHODS: This prospective observational case-control study was conducted in a university ICU during a 2-year period. Patients with VAP (cases) were matched (1:1) to patients without VAP (controls) according to all the following criteria: age, gender, SAPS II, and duration of ICU stay before VAP occurrence. In all patients leptin, C-reactive protein (CRP) and procalcitonin (PCT) were measured at ICU admission, and twice a week. In addition, in cases, leptin, CRP and PCT were also measured on the day of VAP diagnosis. RESULTS: Eighty-six cases were matched with 86 controls. No significant difference was found in leptin and PCT levels between cases and controls. CRP level was significantly higher on the day of VAP in cases compared with controls (99 vs. 48 mg/L, P=0.001). Combination of CRP-leptin (CRP ≥78 mg/L and leptin ≥6.2 ng/mL on the day of VAP) was significantly (P=0.009) associated with VAP in univariate analysis. Multivariate analysis identified the combination of CRP-leptin (OR [95% CI] 3.08 [1.18-8.04], P=0.003), LOD score (1.27 [1.08-1.48], P=0.003), neuromuscular-blockers use (6.6 [2.03-21.7], P=0.002), and reintubation (3.3 [1.14-9.6], P=0.027) as independent risk factors for VAP. CONCLUSION: In our study, leptin level was not associated with VAP occurrence. Further studies are needed to confirm our results, and to define the exact inflammatory role of leptin, and its interest as a biomarker in ICU patients.

Tracheal amylase dosage as a marker for microaspiration: a pilot study.

BACKGROUND: Devices that limit microaspiration through the cuffs of endotracheal tubes could help prevent ventilator-associated pneumonia (VAP). The amount of tracheal microaspirations could be a relevant study endpoint. The aim of our study was to assess whether amylase measured in tracheal secretions constituted a relevant marker for microaspiration. METHODS: Twenty-six patients, intubated for at least 48 h and supplied with a subglottic secretion-suctioning device, constituted a group with a high risk of microaspiration. Twelve non-ventilated patients that required a bronchoscopy procedure constituted a group with a low risk of microaspiration (the control group). Tracheal (T) amylase was compared between the groups. In the intubated group, a series of oral (O), subglottic (Sg) and tracheal (T) suction samples were collected and T/O, T/Sg, Sg/O amylase ratios were determined. RESULTS: Amylase was measured in 277 (89 Sg, 96 B, 92 T) samples from the intubated group and in 12 T samples from the control group. Tracheal amylase was lower in the control group than the intubated group (191 [10-917] vs. 6661 [2774-19,358] IU/L, P<0.001). Amylase gradually increased from tracheal (6661 [2774-19,358] IU/L), to subglottic (130,750 [55,257-157,717] IU/L), to oral samples (307,606 [200,725-461,300] IU/L), resulting in a median 5.5% T/O ratio. In a subset of intubated patients, T amylase samples were assessed in two different laboratories, and gave reproducible results. CONCLUSION: Tracheal amylase was easy to collect, transport, and measure. The T/O amylase ratio is a first step towards quantifying oropharyngeal to tracheal microaspiration in mechanically-ventilated patients.

[Lower respiratory tract infections related to Stenotrophomonas maltophilia and Acinetobacter baumannii]. / Infections bronchopulmonaires à Stenotrophomonas maltophilia et à Acinetobacter baumannii.

Stenotrophomonas maltophilia and Acinetobacter baumannii are both non-fermenting ubiquitous Gram-negative bacilli. The incidence of lower respiratory tract infections related to these microorganisms is increasing, especially in intensive care units. Their capacity to acquire resistance against several antimicrobials is challenging for clinicians and microbiologists. Despite their low virulence, these pathogens are responsible for colonization and infection in patients with comorbidities, immunosuppression, and critically ill patients. S. maltophilia and A. baumannii are mainly identified in nosocomial infections: ventilator-associated pneumonia, bacteremia and surgical wound infection. Infections related to these microorganism are associated with high mortality and morbidity. Trimethoprime-sulfamethoxazole and carbapenem are the first line treatment for infections related to S. maltophilia and A. baumannii respectively. However, the increasing rate of resistance against these agents results in difficulties in treating patients with infections related to these pathogens. New antimicrobial agents and further randomized studies are needed to improve the treatment of these infections. Prevention of spared of these multidrug-resistant bacteria is mandatory, including hand-hygiene, environment cleaning, and limited usage of large spectrum antibiotics.

Risk of acquiring multidrug-resistant Gram-negative bacilli from prior room occupants in the intensive care unit.

The objective of this prospective cohort study was to determine whether admission to an intensive care unit (ICU) room previously occupied by a patient with multidrug-resistant (MDR) Gram-negative bacilli (GNB) increases the risk of acquiring these bacteria by subsequent patients. All patients hospitalized for >48 h were eligible. Patients with MDR GNB at ICU admission were excluded. The MDR GNB were defined as MDR Pseudomonas aeruginosa, Acinetobacter baumannii and extended spectrum ß-lactamase (ESBL) -producing GNB. All patients were hospitalized in single rooms. Cleaning of ICU rooms between two patients was performed using quaternary ammonium disinfectant. Risk factors for MDR P. aeruginosa, A. baumannii and ESBL-producing GNB were determined using univariate and multivariate analysis. Five hundred and eleven consecutive patients were included; ICU-acquired MDR P. aeruginosa was diagnosed in 82 (16%) patients, A. baumannii in 57 (11%) patients, and ESBL-producing GNB in 50 (9%) patients. Independent risk factors for ICU-acquired MDR P. aeruginosa were prior occupant with MDR P. aeruginosa (OR 2.3, 95% CI 1.2-4.3, p 0.012), surgery (OR 1.9, 95% CI 1.1-3.6, p 0.024), and prior piperacillin/tazobactam use (OR 1.2, 95% CI 1.1-1.3, p 0.040). Independent risk factors for ICU-acquired A. baumannii were prior occupant with A. baumannii (OR 4.2, 95% CI 2-8.8, p <0.001), and mechanical ventilation (OR 9.3, 95% CI 1.1-83, p 0.045). Independent risk factors for ICU-acquired ESBL-producing GNB were tracheostomy (OR 2.6, 95% CI 1.1-6.5, p 0.049), and sedation (OR 6.6, 95% CI 1.1-40, p 0.041). We conclude that admission to an ICU room previously occupied by a patient with MDR P. aeruginosa or A. baumannii is an independent risk factor for acquisition of these bacteria by subsequent room occupants. This relationship was not identified for ESBL-producing GNB.

Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood.

Early diagnosis of sepsis, rapid identification of the causative pathogen(s) and prompt initiation of appropriate antibiotic treatment have a combined impact on mortality due to sepsis. In this observational study, a new DNA-based system (LightCycler SeptiFast (LC-SF) test; Roche Diagnostics) allowing detection of 16 pathogens at the species level and four groups of pathogens at the genus level has been evaluated and compared with conventional blood cultures (BCs). One hundred BC and LC-SF results were obtained for 72 patients admitted to the intensive-care unit over a 6-month period for suspected sepsis. Microbiological data were compared with other biological parameters and with clinical data. The positivity rate of BCs for bacteraemia/fungaemia was 10%, whereas the LC-SF test allowed detection of DNA in 15% of cases. The LC-SF performance, based on its clinical relevance, was as follows: sensitivity, 78%; specificity, 99%; positive predictive value, 93%; and negative predictive value, 95%. Management was changed for four of eight (50%) of the patients because organisms were detected by the LC-SF test but not by BC. LC-SF results were obtained in 7-15 h, in contrast to the 24-72 h required for BC. According to the LC-SF results, initial therapy was inadequate in eight patients, and antibiotic treatment was changed. Our results suggest that the LC-SF test may be a valuable complementary tool in the management of patients with clinically suspected sepsis.

Accuracy of American Thoracic Society/Infectious Diseases Society of America criteria in predicting infection or colonization with multidrug-resistant bacteria at intensive-care unit admission.

The aim of this prospective observational study was to determine the accuracy of American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) criteria in predicting infection or colonization related to multidrug-resistant (MDR) bacteria at intensive-care unit (ICU) admission. MDR bacteria were defined as methicillin-resistant Staphylococcus aureus, ceftazidime-resistant or imipenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and extended-spectrum ß-lactamase-producing Gram-negative bacilli. Screening for MDR bacteria (using nasal and rectal swabs and tracheal aspirates from intubated patients) was performed at ICU admission. Risk factors for infection or colonization with MDR bacteria at ICU admission were determined using univariate and multivariate analyses. The accuracy of ATS/IDSA criteria in predicting infection or colonization with these bacteria at ICU admission was calculated. Eighty-three (13%) of 625 patients were infected or colonized with MDR bacteria at ICU admission. Multivariate analysis allowed identification of prior antimicrobial treatment (OR 2.3, 95% CI 1.2-4.3; p 0.008), residence in a nursing home (OR 2, 95% CI 1.1-3.7; p <0.001), and prior hospitalization (OR 3.9, 95% CI 1.7-8.8; p <0.001) as independent predictors of infection or colonization with MDR bacteria at ICU admission. Although sensitivity (89%) and negative predictive values (96%) were high, low specificity (39%) and a positive predictive value (18%) were found when ATS/IDSA criteria were used in predicting infection or colonization with MDR bacteria at ICU admission. In patients with pneumonia, adherence to guidelines was associated with increased rates of appropriate initial antibiotic treatment and de-escalation. ATS/IDSA criteria had an excellent negative predictive value and a low positive predictive value concerning infection or colonization with MDR bacteria at ICU admission.

Antibodies against glucan, chitin, and Saccharomyces cerevisiae mannan as new biomarkers of Candida albicans infection that complement tests based on C. albicans mannan.

Antibodies against Saccharomyces cerevisiae mannan (ASCA) and antibodies against synthetic disaccharide fragments of glucans (ALCA) and chitin (ACCA) are biomarkers of Crohn's disease (CD). We previously showed that Candida albicans infection generates ASCA. Here, we explored ALCA and ACCA as possible biomarkers of invasive C. albicans infection (ICI). ASCA, ALCA, ACCA, and Candida mannan antigen and antibody detection tests were performed on 69 sera obtained sequentially from 18 patients with ICIs proven by blood culture, 59 sera from CD patients, 47 sera from hospitalized subjects colonized by Candida species (CZ), and 131 sera from healthy controls (HC). ASCA, ALCA, and ACCA levels in CD and ICI patients were significantly different from those in CZ and HC subjects (P<0.0001). In ICI patients, these levels increased as infection developed. Using ASCA, ALCA, ACCA, and Platelia Candida tests, 100% of ICIs were detected, with the kinetics of the antibody response depending on the patient during the time course of infection. A large number of sera presented with more than three positive tests. This is the first evidence that the detection of antibodies against chitin and glucans has diagnostic value in fungal infections and that these tests can complement more specific tests. Future trials are necessary to assess the value of these tests in multiparametric analysis, as well as their pathophysiological relevance.

[Pseudomonas aeruginosa and Candida albicans interaction in the respiratory tract: from pathophysiology to a therapeutic perspective]. / Interaction de Pseudomonas aeruginosa avec Candida albicans dans les voies respiratoires: de la physiopathologie à une perspective thérapeutique.

Several studies evidenced a pathogenic interaction between P. aeruginosa and C. albicans. P. aeruginosa is one of the most frequent microorganisms responsible for ventilator-associated pneumonia (VAP) and C. albicans usually colonize tracheo-bronchial tract of patients undergoing mechanical ventilation in the intensive care unit. In vitro, P. aeruginosa exploits filamentous fungi resulting in fungal killing and limitation of C. albicans growth in the host. Biofilm also play an important role as a persistent source of infectious material for recurrent episodes of VAP. Indeed, Candida spp and P. aeruginosa are the most common pathogens retrieved from endotracheal tube biofilm and tracheal secretions in patients with VAP. Finally, it has been demonstrated that previous tracheo-bronchial C. albicans colonization enhanced the incidence of P. aeruginosa pneumonia in a murine model. A recent study performed in patients requiring intubation and mechanical ventilation identified Candida spp tracheo-bronchial colonization as a risk factor for P. aeruginosa VAP. In addition, a retrospective study suggested that antifungal treatment might reduce P. aeruginosa VAP or tracheo-bronchial colonization in intubated patients with Candida spp tracheo-bronchial colonization. These interactions have major environmental and medical consequences. Experimental studies providing a better understanding of the mechanisms of interaction and clinical studies evaluating the necessity of a antifungal treatment might improve the management of these opportunistic infections.

[Ventilator-associated pneumonia and chronic obstructive pulmonary disease]. / Pneumonies acquises sous ventilation mécanique invasive et bronchopneumopathie chronique obstructive.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a common pulmonary and systemic inflammatory disease. Patients with COPD frequently require mechanical ventilation for acute exacerbations. BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) in COPD patients varies from 6 to 33%. Tracheo-bronchial colonisation, local and systemic immuno-supression and frequent antibiotic treatment are factors predisposing to VAP in these patients. Gram negative bacilli are commonly isolated in COPD patients with VAP. Pseudomonas aeruginosa reported to be the most common. The diagnosis of VAP can be difficult in patients with COPD because of the low sensitivity of the portable chest radiograph. VAP is associated with higher mortality rates, longer duration of mechanical ventilation and ITU stay in patients with COPD. Initial antibiotic treatment should be based on recent guidelines and should take account of frequent prior hospitalisation and antibiotic treatment which are well known risk factors for multidrug resistant bacteria. Preventative measures recommended for the general population should be applied to COPD patients. In the absence of contraindications the use of non-invasive ventilation is recommended to reduce the risk of VAP. VIEWPOINT AND CONCLUSION: Future studies should better determine the incidence of VAP in COPD, improve the diagnostic approach and determine the effects of treating malnutrition, chronic tracheobronchial colonisation and limiting antibiotic and corticosteroid treatment on the incidence of VAP.

Relationship between tracheotomy and ventilator-associated pneumonia: a case control study.

The aim of the present study was to determine the relationship between tracheotomy and ventilator-associated pneumonia (VAP). The study used a retrospective case-control study design based on prospective data. All nontrauma immunocompetent patients, intubated and ventilated for >7 days, were eligible for inclusion in the study. A diagnosis of VAP was based on clinical, radiographical and microbiological criteria. Four matching criteria were used, including duration of mechanical ventilation (MV). The indication and timing of tracheotomy were at the discretion of attending physicians. Univariate and multivariate analyses were performed to determine risk factors for VAP in cases (patients with tracheotomy) and controls (patients without tracheotomy). In total, 1,402 patients were eligible for inclusion. Surgical tracheotomy was performed in 226 (16%) patients and matching was successful for 177 (78%). The rate of VAP (22 versus 14 VAP episodes.1,000 MV-days(-1)) was significantly higher in controls than in cases. The rate of VAP after tracheotomy in cases, or after the corresponding day of MV in controls, was also significantly higher in control than in case patients (9.2 versus 4.8 VAP episodes.1,000 MV-days(-1)). In multivariate analysis, neurological failure (odds ratio (95% confidence interval) 2.7 (1.3-5)), antibiotic treatment (2.1 (1.1-3.2)) and tracheotomy (0.18 (0.1-0.3)) were associated with VAP. In summary, the present study demonstrates that tracheotomy is independently associated with decreased risk for ventilator-associated pneumonia.

[Acute invasive pulmonary aspergillosis in chronic lung disease--a review]. / Aspergillose pulmonaire aiguë invasive et pathologies pulmonaires chroniques.

INTRODUCTION: Apart from malignancies and solid organ transplant, chronic lung disease, in particular chronic obstructive pulmonary disease (COPD), is a third important predisposing factor for acute invasive pulmonary aspergillosis. STATE OF THE ART: COPD is present in 2% of patients dying from invasive aspergillosis. This opportunistic infection occurs because of an immunodeficiency linked both to altered local immunity and to systemic factors such as long term steroid treatment and malnutrition. In patients whose sputum and/or endotracheal aspirate specimens contain hyphal forms of filamentous Aspergillus, half will have a clinically significant aspergillus infection. Diagnostic tests include serum galactomannan antigen test, serum antibody titre, thoracic CT scan and bronchoalveolar lavage (BAL). The identification of fungal hyphae in BAL fluid by microscopy and/or on culture is critical for a positive diagnosis. The mortality rate for acute invasive pulmonary aspergillosis in chronic lung diseases reaches almost 100%. Antifungal monotherapy is still recommended as a first line treatment. Combined treatment can be used in refractory aspergillosis as a salvage therapy. The question of maintaining, decreasing or interrupting steroid treatment must be considered. PERSPECTIVES: Prospective studies are needed to evaluate a standardised diagnostic strategy such as exists for patients with haematological disease. Whether this will improve prognosis remains to be seen. CONCLUSION: Acute invasive pulmonary aspergillosis complicating chronic lung disease is not rare. Improved diagnosis procedures and recent therapeutic advances may have a positive impact on patient prognosis.

[Impact of fluoroquinolone use on multidrug-resistant bacteria emergence]. / Impact de l'utilisation des fluoroquinolones sur l'émergence des bactéries multirésistantes.

During the last two decades, fluoroquinolone use has significantly increased in Europe and in the USA. This could be explained by the arrival of newer fluoroquinolones with antipneumoccal activity. Increased use of fluoroquinolones is associated with higher rates of bacterial resistance to these antibiotics. Resistance of Gram-negative bacilli to fluoroquinolones is increasing in industrialized countries. In addition, fluoroquinolone use has been identified as a risk factor for colonization and infection to methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanni, extending-spectrum beta-lactamase producing Gram negative bacilli, and multidrug-resistant bacteria. Nosocomial infections due to multidrug-resistant bacteria are associated with higher mortality and morbidity rates. This could be related to more frequent inappropriate initial antibiotic treatment in these patients. Limiting the use of fluoroquinolones, limiting the duration of treatment with fluoroquinolones, and using appropriate dosage of these antibiotics could be suggested to reduce resistance to these antibiotics and to reduce the emergence of multidrug-resistant bacteria.