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There is no consensus on optimal screening procedures for multidrug-resistant Enterobacteriaceae (MDRE) in intensive care units (ICUs). Therefore, we assessed five strategies for the detection of extended-spectrum beta-lactamase (ESBL) and high-level expressed AmpC cephalosporinase (HL-CASE) producers. During a 3-month period, a rectal screening swab sample was collected daily from every ICU patient, from the first 24 h to the last day of ICU stay. Samples were plated on MDRE-selective media. Bacteria were identified using MALDI-TOF mass spectrometry and antibiograms were performed using disk diffusion. MDREs were isolated from 682/2348 (29.0%) screening samples collected from 93/269 (34.6%) patients. Incidences of patients with ESBL and HL-CASE producers were 17.8 and 19.3 per 100 admissions, respectively. In 48/93 patients, MDRE carriage was intermittent. Compared with systematic screening at admission, systematic screening at discharge did not significantly increase the rate of MDRE detection among the 93 patients (62% vs. 70%). In contrast, screening at admission and discharge, screening at admission and weekly thereafter, and screening at admission and weekly thereafter and at discharge significantly increased MDRE detection (77%, p 0.02; 76%, p 0.01; 86%, p<0.001, respectively). The difference in MDRE detection between these strategies relies essentially on the levels of detection of patients with HL-CASE producers. The most reasonable strategy would be to collect two samples, one at admission and one at discharge, which would detect 87.5% of the ESBL strains, 67.3% of the HL-CASE strains and 77.4% of all MDRE strains. This study should facilitate decision-making concerning the most suitable screening policy for MDRE detection in a given ICU setting., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Nosocomial pneumonia occurs in 0.5 to 1.5% of all hospitalized patients and in 10 to 30% of those under artificial ventilation. The main causal agents are Staphylococcus aureus and resistant Gram-negative bacilli, particularly Pseudomonas aeruginosa. In case of early onset (before the fifth day), Haemophilus influenzae, Streptococcus pneumoniae and susceptible enterobacteria predominate. These infections are associated with overmortality, particularly in patients with P. aeruginosa pneumonia, severe respiratory failure, shock syndrome or given a poorly adapted antibiotic regimen. Management of patients with nosocomial pneumonia depends on the clinical presentation and prior bacteriology data often leading to empiric antibiotic prescription. Published guidelines, for example those recommended by the American Thoracic Society, can also be used to adapt the antibiotic therapy as a function of the severity of the clinical situation, the patient's comorbidities, and the date of onset. This type of strategy remains to be evaluated. It would be advisable to base therapeutic management on reliable microbiological data allowing selection of patients requiring antibiotics and treatment based on culture results. Currently a two-drug regimen is recommended for nosocomial pneumonia due to P. aeruginosa or particularly resistant strains.

Background: Optimal management of patients who are clinically suspected of having ventilator-associated pneumonia remains open to debate., Objective: To evaluate the effect on clinical outcome and antibiotic use of two strategies to diagnose ventilator-associated pneumonia and select initial treatment for this condition., Design: Multicenter, randomized, uncontrolled trial., Setting: 31 intensive care units in France., Patients: 413 patients suspected of having ventilator-associated pneumonia., Intervention: The invasive management strategy was based on direct examination of bronchoscopic protected specimen brush samples or bronchoalveolar lavage samples and their quantitative cultures. The noninvasive ("clinical") management strategy was based on clinical criteria, isolation of microorganisms by nonquantitative analysis of endotracheal aspirates, and clinical practice guidelines., Measurements: Death from any cause, quantification of organ failure, and antibiotic use at 14 and 28 days., Results: Compared with patients who received clinical management, patients who received invasive management had reduced mortality at day 14 (16.2% and 25.8%; difference, -9.6 percentage points [95% CI, -17.4 to -1.8 percentage points]; P = 0.022), decreased mean Sepsis-related Organ Failure Assessment scores at day 3 (6.1+/-4.0 and 7.0+/-4.3; P = 0.033) and day 7 (4.9+/-4.0 and 5.8+/-4.4; P = 0.043), and decreased antibiotic use (mean number of antibiotic-free days, 5.0+/-5.1 and 2.2+/-3.5; P < 0.001). At 28 days, the invasive management group had significantly more antibiotic-free days (11.5+/-9.0 compared with 7.5+/-7.6; P < 0.001), and only multivariate analysis showed a significant difference in mortality (hazard ratio, 1.54 [CI, 1.10 to 2.16]; P = 0.01)., Conclusions: Compared with a noninvasive management strategy, an invasive management strategy was significantly associated with fewer deaths at 14 days, earlier attenuation of organ dysfunction, and less antibiotic use in patients suspected of having ventilator-associated pneumonia.

Nosocomial pneumonia is a frequent complication in hospitalized patients. Gram-positive pathogens, particularly Staphylococcus aureus, are responsible for the increasing frequency of nosocomial pneumonia. To evaluate the efficacy and safety of intravenous quinupristin/dalfopristin (Synercid) in the treatment of nosocomial pneumonia caused by gram-positive pathogens we conducted a prospective, randomized, open-label, international, multicenter, comparative clinical trial. Two hundred ninety-eight patients with nosocomial pneumonia were enrolled in 74 active centers in five countries: a subgroup of 171 (87 quinupristin/dalfopristin-treated and 84 vancomycin-treated patients) were evaluable for the major efficacy end points. One hundred fifty received 7.5 mg/kg of quinupristin/dalfopristin every 8 h; 148 patients received 1 g of vancomycin every 12 h. Aztreonam at a dose of 2 g every 8 h could be administered in both groups for coverage of gram-negative organisms, and tobramycin was added for coverage against Pseudomonas aeruginosa. The primary efficacy end point was the clinical response between the seventh and the thirteenth day after the end of treatment in clinically evaluable patients with documented causative pathogen(s) at baseline (bacteriologically evaluable population). Therapy was clinically successful (cure or improvement) in 49 (56.3%) of patients receiving quinupristin/dalfopristin and 49 (58.3%) patients receiving vancomycin (difference, -2.0% [95% CI, -16.8% to 12.8%]) in the bacteriologically evaluable population. Equivalent clinical success rates were also observed in the all-treated population (n = 298), and in the bacteriologically evaluable patients intubated in baseline (39/72 [54%] compared with 36/67 [54%]). The by-pathogen bacteriologic response was similar in both treatment groups, with equivalent clinical success rates for Streptococcus pneumoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus. Adverse events (venous and nonvenous) were equally distributed between groups; 15.3% of quinupristin/dalfopristin patients and 9.5% of vancomycin patients discontinued therapy because of an adverse clinical event. In this study quinupristin/dalfopristin was shown to be equivalent to vancomycin in the treatment of nosocomial pneumonia caused by gram-positive pathogens. Quinupristin/dalfopristin merits further evaluation for the treatment of nosocomial pneumonia caused by methicillin-resistant S. aureus.

To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment. Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations. Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered. Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection. Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01). These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients. However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients. When follow-up PSB cultures were negative, an improved outcome was noted.