Factors associated with hospital mortality in community-acquired legionellosis in France.

The aims of this study were to describe the clinical, biological and radiological features of community-acquired (CA) Legionnaires' disease (LD) and identify the predictors of mortality in hospitalised patients. Demographic data, risk factors, clinical and biological features, medical management, complications, and outcome from 540 hospitalised patients with confirmed CA LD were prospectively recorded. 8.1% of patients (44 out of 540) died. The predictors of survival after Kaplan-Meier analysis were male sex (p = 0.01), age <60 yrs (p = 0.02), general symptoms (p = 0.006), intensive care unit (ICU) stay (p<0.001), and class II-III Pneumonia Severity Index score (p = 0.004). Six predictors of death were identified by multivariate analysis: age (per 10-yr increment) (relative hazard (RH) 1.50, 95% CI 1.21-1.87), female sex (RH 2.00, 95% CI 1.08-3.69), ICU admission (RH 3.31, 95% CI 1.67-6.56), renal failure (RH 2.73, 95% CI 1.42-5.27), corticosteroid therapy (RH 2.54, 95% CI 1.04-6.20) and C-reactive protein (CRP) >500 mg · L(-1) (RH 2.14, 95% CI 1.02-4.48). Appropriate antibiotic therapy was prescribed for 70.8% (292 out of 412) of patients after admission and for 99.8% (537 out of 538) of patients after diagnosis confirmation. In conclusion, female sex, age, ICU stay, renal failure, corticosteroid treatment and increased level of CRP are significant risk factors for mortality in CA LD.

[Interest of real-time PCR Xpert MRSA/SA on GeneXpert(®) DX System in the investigation of staphylococcal bacteremia]. / Intérêt de la PCR temps réel Cepheid Xpert SAMR/SA sur GeneXpert(®) DX System dans la prise en charge de la bactériémie à staphylocoque.

AIM OF THE STUDY: Recently, a rapid, fully automated real-time PCR test has become available for detection of Staphylococcus aureus in positive blood cultures, Xpert MRSA/SA blood culture. This study was defined to evaluate the use of this product in our hospital setting to assist in optimizing antibiotic treatment. MATERIALS AND METHODS: Over a period of 18months (from February 2008 to July 2009), 51 positive blood cultures were examined for Staphylococcus using the Xpert MRSA/SA assay on the GeneXpert(®) System. The PCR results were transferred to the clinician as soon as available. The presence of empirical antibiotic therapy was noted and modified if necessary after discussions between the clinician and the infectious disease specialist. RESULTS: Twenty-three blood bottles were positive for S. aureus, two were resistant to methicillin. Twenty-eight were coagulase negative staphylococci. No discrepancy between identification (S. aureus) and methicillin resistance was observed. Thirty-two samples had clinically significant bacteremia (23 S. aureus and nine coagulase negative staphylococci). Sixteen (50%) of these patients had received inappropriate antibiotic therapy (11 without antibiotic therapy, five with betalactam antibiotics). For these patients, an appropriate antibiotic therapy was prescribed according to these results. Sixteen patients had adequate empirical antibiotic therapy at the time of receiving the PCR result. Among these 16 patients, eight switches were performed from broad-spectrum treatment to a more restrictive antistaphylococcal treatment. Of the 19 patients with a nonclinically relevant coagulase negative staphylococci infection, four were already on antibiotics for other infections and these treatments were not modified. Empirical treatment could be avoided in 13 patients who had a clinical presentation consistent with staphylococcal bacteremia (multiple sores, history of carrying methicllin-resistant or susceptible S. aureus infection, presence of intravascular material or prosthesis). CONCLUSION: The real-time PCR Cepheid Xpert MRSA/SA on GeneXpert(®) DX System has become an essential tool in our laboratory enhancing the reports of positive blood cultures for staphylococci. This test is fast (50min) and reliable. It allows optimization of antibiotic therapy in hospital.

[Invasive candidiasis in ICU: analysis of antifungal treatments in the French study AmarCand]. / Candidoses invasives en réanimation: analyse des traitements antifongiques au cours de l'enquête française AmarCand.

OBJECTIVE: Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines. STUDY DESIGN: Prospective, observational, French multicenter study (October 2005-May 2006). PATIENTS AND METHODS: Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis. RESULTS: One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida. CONCLUSION: The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.

[Profile of patients facing therapeutic problems in nosocomial infections due to methicillin-resistant staphylococci--A survey of practices]. / Profil des patients en situation de difficulté thérapeutique dans les infections nosocomiales à staphylocoque résistant à la méticilline. Enquête de pratique.

Methicillin-resistant staphylococcal infections (MRSI) are still common in an intensive care setting. Their management is mainly based on glycopeptides, combined with other antibiotics when this is possible, and also on treatment of the portal of entry (removal of foreign bodies, surgery...). Implementation of this antibiotic therapy may meet with difficulties linked to the micro-organism (existence of strains with diminished sensitivity to glycopeptides), to the toxicity of glycopeptides or to the unfavourable course of the infection. A survey of practices was performed on a representative sample of 240 intensive care units in France. Glycopeptides, and particularly vancomycin, were the most frequently employed and prescribed in combination with other compounds. Therapeutic problems were considered as occasional, their incidence ranging from 0 to 50%. The problems reported were mainly linked to adverse effects: most frequently renal toxicity and, to a lesser extent, immunological and allergic complications. Diminished sensitivity to glycopeptides was only reported by a third of physicians, and this sporadically. Such a survey of practices is an essential preliminary to an epidemiological study of the incidence of MRSI and related therapeutic problems.

Impact of appropriateness of initial antibiotic therapy on the outcome of ventilator-associated pneumonia.

OBJECTIVES: To evaluate the impact of appropriate initial antibiotic therapy (AB) on the outcome of ventilator-associated pneumonia (VAP). DESIGN: Retrospective study (1992-97). PATIENTS AND METHODS: Episodes of VAP diagnosed on both clinical and microbiological criteria after > or = 48 h of mechanical ventilation (MV). Initial AB was considered appropriate when all significant organisms were susceptible to at least one of the antibiotics started after distal bronchial sampling. Antibiotic treatment was modified within 48 h when susceptibility testing was available. Outcome was recorded at the ICU and hospital discharge. RESULTS: One hundred and eleven patients were included (SAPS II = 48 +/- 18, age = 62 +/- 14 years, mean duration of MV before VAP = 12 +/- 9 days). Initial AB was appropriate in 55 patients (49.5%). No difference between appropriate initial AB and inappropriate initial AB was found concerning severity indices at the time of VAP diagnosis. ICU length of stay was shorter with appropriate initial AB than with inappropriate initial AB for survivors (12 +/- 11 days vs 20 +/- 24 days, P = 0.01). Crude hospital mortality tended to be lower with appropriate initial AB than with inappropriate initial AB (47.3% vs 60.7%, odds ratio = 1.72, 95% CI = 0.81-3.7). Relative crude mortality reduction with appropriate initial AB was 22%, 95% CI = -10% to 45%. CONCLUSION: Inappropriate initial AB of VAP during the first 48 h increased ICU length of stay after VAP diagnosis and tended to increase crude hospital mortality despite equal severity of illness at the time of VAP diagnosis, when compared to appropriate initial AB in a population of 111 ICU patients.

Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia. A randomized trial.

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.

[Tuberculous meningitis in an immunocompetent adult: contribution of cerebral imaging techniques to the diagnosis and follow-up]. / Méningite tuberculeuse de l'adulte sans immunodépression acquise: contribution de l'imagerie cérébrale au diagnostic et au suivi évolutif.

We have studied 5 men, mean age 47 years, affected by tuberculous meningitis (TM) without documented immunodepression. The diagnosis of TM was supported by clinical and biological investigations and confirmed by the cultures of CSF. All the patients received a four-drug combination therapy and steroids. No drug resistance of the bacilli was observed. Cerebral imaging by CT and MRI was rarely diagnostic but most useful during the follow-up. All the patients developed complications including tuberculomas (5), hydrocephalus (4), ischemic lesions (2), arachnoiditis (1) and abscess of spinal cord (1). Four patients recovered and one died. The mean duration of the follow-up was 16 months. MRI was more sensitive than CT scan to identify inflammatory lesions such as granulomas, angeitis or arachnoiditis and to follow their outcome. Tuberculomas and hydrocephalus were easily diagnosed by CT scan with contrast enhancement. Recommendations of sequential imaging are suggested to identify unexpected or asymptomatic complications of TM during therapy and evaluate the outcome.

Treatment of ventilator-associated pneumonia with piperacillin-tazobactam/amikacin versus ceftazidime/amikacin: a multicenter, randomized controlled trial. VAP Study Group.

In a randomized trial conducted in 27 intensive care units, we compared the clinical efficacy and safety of piperacillin-tazobactam (TAZ; 4 g/0.5 g q.i.d.) and of ceftazidime (CAZ; 1 g q.i.d.), both combined with amikacin (7.5 mg/kg b.i.d.), as therapy for ventilator-associated pneumonia (VAP; acquired after > or =48 hours of mechanical ventilation). VAP was diagnosed with use of protected samples and quantitative cultures, and outcome was assessed blindly from treatment. Of 204 patients suspected of having VAP and randomized to a treatment arm of the study, 127 (64%) had bacteriologically confirmed infections, of which 37% were polymicrobial and 32% involved Pseudomonas aeruginosa; 115 patients (51 TAZ and 64 CAZ recipients) remained evaluable as per protocol. Clinical/bacteriologic cure rates (TAZ vs. CAZ, 51% vs. 36%; 95% confidence interval of difference, -0.2% to 30.2%), and 28-day mortality rates (16% vs. 20%) were similar; however, fewer bacteriologic failures occurred with TAZ (33% vs. 51%; P = .05). We conclude that the two regimens were of equivalent clinical efficacy in therapy for confirmed VAP.

Confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram-negative bacterial sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. BN 52021 Sepsis Investigator Group.

OBJECTIVE: To determine the efficacy and safety of using natural platelet-activating factor receptor antagonist (PAFra), BN 52021, to treat patients with severe Gram-negative bacterial sepsis. DESIGN: A prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. SETTING: Fifty-nine academic medical center intensive care units in Europe. PATIENTS: Six hundred nine patients with severe sepsis, suspected to be related to Gram-negative bacterial infection, who received PAFra or placebo. INTERVENTIONS: Patients were randomized to receive either a dose of PAFra (120 mg iv) every 12 hrs over a 4-day period or placebo over a 4-day period. MEASUREMENTS AND MAIN RESULTS: The patients were well matched at study entry for severity of illness and for risk factors known to influence the outcome of sepsis. Among all randomized patients, the 28-day, all-cause mortality rate was 49% (152/308) in the placebo group, and 47% (140/300) in the PAFra group (p=.50). When analyzed on the basis of the previously defined target population, the 28-day, all-cause mortality rate was 50% (115/232) in the placebo group and 44% (94/212) in the PAFra group, yielding a 12% reduction in mortality rate (p=.29). In patients with documented infection involving other organisms, there was no difference between treated and placebo groups. When the outcomes of organ dysfunctions were examined in the overall population and in the documented Gram-negative bacterial infection population, the number of patients who resolved hepatic dysfunction tended to be higher in the treated group than in the placebo group (p=.06). The number of adverse events reported were not different between the two groups. CONCLUSIONS: A 4-day administration of the studied PAFra (BN 52021) failed to demonstrate a statistically significant reduction in the mortality rate of patients with severe sepsis suspected to be related to Gram-negative bacterial infection. If PAFra treatment has any therapeutic activity in severe Gram-negative bacterial sepsis, the incremental benefits are small and will be difficult to demonstrate in a patient population as defined by this clinical trial.

Diarrhea in intensive care: diagnosis and treatment.

Diarrhea is a common complication in critically ill patients. The use of ready-to-use sterile formulas, disposable feeding lines, and flow regulated pumps should decrease the frequency of diarrhea due to enteral nutrition. Antimicrobial agents are an important cause of diarrhea, because they modify the digestive flora and may induce Clostridium difficile colitis. Occurrence of diarrhea is also correlated with several factors reflecting the severity of the underlying disease, such as shock and sepsis. Treatment of diarrhea includes rehydratation, agents that delay transit, restoration of a normal flora, treatment of a specific cause and of the underlying disease.

Iatrogenic complications in adult intensive care units: a prospective two-center study.

OBJECTIVES: a) To evaluate the frequency, types, severity, and morbidity of iatrogenic complications; b) determine associated factors that favor iatrogenic complications; and c) suggest new or more efficient protective measures that may be taken to improve patient safety. DESIGN: Prospective, observational study. SETTING: Two ICUs in France. PATIENTS AND METHODS: The study included 382 patients (age > or = 15 yrs; 400 consecutive admissions). Patients were monitored by two physicians in each ICU to assess all iatrogenic complications occurring during their ICU stay, with the exception of adverse effects of drugs. An iatrogenic complication was defined as an adverse event that was independent of the patient's underlying disease. RESULTS: We observed 316 iatrogenic complications in 124 (31%) of the 400 admissions. Of these iatrogenic complications, 107 (in 53 [13%] of the 400 admissions) complications were major, three leading to death. Severe hypotension, respiratory distress, pneumothorax, and cardiac arrest represented 78% of the major iatrogenic complications. Fifty-nine percent of the major iatrogenic complications had clearly identified associated factors. Human errors accounted for 67% of these factors. Patients > 65 yrs (adjusted odds ratio = 2.6, 95% confidence interval: 1.4 to 4.9) and those patients admitted with two or more organ failures (adjusted odds ratio = 4.8, 95% confidence interval: 2.5 to 9.2) were more likely to develop major iatrogenic complications. High or excessive nursing workload also led to an increased risk of major iatrogenic complications. Persistent morbidity, secondary to iatrogenic complications at the time of discharge, was present in five survivors. The risk of ICU death was about two-fold higher for the patients with major iatrogenic complications than in the remaining patients after adjusting for the Organ System Failure Score and the prognosis of the disease (relative risk = 1.92, 95% confidence interval: 1.28 to 2.56). CONCLUSIONS: Major iatrogenic complications were frequent, associated with increased morbidity and mortality rates, related to high or excessive nursing workload, and were often secondary to human errors. To improve patient safety in our ICUs, preventive measures should be targeted primarily on the elderly and the most severely ill patients. Special attention should be given to improving the organization of workload and training, and promoting wider use of noninvasive monitoring.

An open multicentre study of the efficacy and tolerance of cefodizime 1 g bd intravenously or intramuscularly in lower respiratory tract infections.

The efficacy and tolerance of cefodizime in lower respiratory tract infections in hospitalized adults was evaluated in an open, non-comparative multicentre trial. Cefodizime (HR 221), was administered as a dose of 1 g by slow iv or im injection every 12 h (2 g daily) to 301 hospitalized patients aged 18-91 years. The mean duration of treatment was 10 +/- 3 days (median 9, range 1.23). All 301 patients were evaluable for tolerance, 270 were evaluable for clinical efficacy, and 204 were evaluable for bacteriological efficacy. A satisfactory clinical response was achieved in 87.8% (237/270) of patients and a satisfactory bacteriological response in 90.2% (184/204). Of the patients given the drug iv, 3.9% (6/153) had pain at the site of the injection compared with 7.4% (11/148) of those given the drug im. Tolerance was good; only five patients experienced an adverse reaction, and a relationship with cefodizime was considered probable in four of these cases. Haematological, hepatic and renal function tests revealed 27 abnormalities, all considered to have a doubtful relationship with treatment.

Comparison of the activity of three antibiotic regimens in severe Legionnaires' disease.

Comparison of the activity of different antibiotic regimens in Legionnaire's disease has never been made because of the rarity of well documented cases of that disease. We have retrospectively compared severe cases of Legionnaires' disease treated with pefloxacin alone or in combination with erythromycin and/or rifampicin using computer-matched cases treated either with erythromycin or with erythromycin in combination with rifampicin. This study suggests that: (1) combined therapy including erythromycin, rifampicin and/or pefloxacin is superior to therapy with erythromycin alone; (2) combinations including pefloxacin may be the most active ones; and (3) pefloxacin alone may be as active as combination therapy. Although these results are in agreement with data obtained in cell and in animal models of legionella infection they need to be further confirmed by the study of larger number of patients.

Decreased paradoxic pulse from increased venous return in severe asthma.

During severe asthma, paradoxic pulse may result from increased impedance to left ventricular ejection, mechanical impairment of left ventricular filling by ventricular interdependence or decreased pulmonary venous return augmented by hypovolemia. We studied the effect of reversible blood volume expansion by MAST inflation during severe attacks of asthma. Ten patients with clinically detectable paradoxic pulse of more than 20 mm Hg were studied. All had a history of reversible bronchial asthma with evidence of respiratory and circulatory failure. Standard therapy for asthma was started. We observed no difference in respiratory and heart rates during MAST inflation. Paradoxic pulse was consistently decreased during MAST inflation; paradoxic pulse returned to baseline values after MAST deflation. The decrease in paradoxic pulse was produced by an increased inspiratory systolic arterial pressure. We conclude that a reduction in pulmonary venous return is more important than ventricular interdependence in producing paradoxic pulse during severe asthma.