Impact of a five-year surveillance of central venous catheter infections in the REACAT intensive care unit network in France.

Central venous catheter (CVC)-related infections (CRIs) are a key target for infection control in intensive care units (ICUs). The aim of this study was to describe temporal trends of CRI incidence in a network of volunteer ICUs in Northern France. During a 4 month surveillance period each year, all CVCs in place for more than 48h were prospectively followed until removal or patient discharge. Standard clinical and microbiological criteria were used to define colonization and CRI. The standardized incidence ratio (SIR) was estimated by dividing the number of observed CRIs by the number of expected CRIs, which was computed using a logistic regression model including risk factors for CRI. CRI incidence and SIR were fed back to ICUs as a benchmark at the end of each period. From 2001 to 2005, 135 ICUs participated for at least one surveillance period. Overall, 11 703 CVC in 9182 patients (122 495 CVC-days) were included. CRI incidence was 2.8 per 1000 CVC-days. Among 35 ICUs that participated for three or more consecutive periods, CRI incidence decreased significantly by 58.6%. SIR also decreased significantly from the first to the third surveillance period in these ICUs. These results suggest that surveillance programmes have a significant impact on CRI risk in ICUs and remain an important strategy for combating nosocomial infections in these settings.

[Evaluation of the antibiotic prescription in a paediatric intensive care unit]. / Evaluation de la prescription antibiotique dans un service de réanimation pédiatrique.

UNLABELLED: The antibiotic prescription in intensive care units is frequent using often broad-spectrum antibiotics; its quality has never been evaluated in paediatric intensive care units. OBJECTIVES: To describe the modalities of antibiotic prescriptions in a paediatric intensive care unit and confront them to the literature guidelines and bacteriological data. METHODS: From January 1st to March 31st 2005, 52 consecutive prescriptions regarding 45 children, with a total of 47 hospitalisations were prospectively analysed. RESULTS: Confirmed diagnosis of bacterial infection was retained for 50 of the 52 patients: community acquired infection in 35 cases (70%) and a nosocomial infection in 15 cases. Ten children died during the antibiotic treatment (22%), with 5 deaths related to the infection (11%). Monotherapy represented 56% of the prescriptions of antibiotics. The initial antibiotic treatment was empirical in 42 of 52 cases (81%). The empirical prescriptions were documented afterward in 48% of cases. One or more microorganisms were isolated for 60% of the initial prescriptions. Misuses in antibiotic doses (in excess [10%] or by insufficiency [13%]), number of daily administration (4%), and way of administration and/or length of treatment were observed. Seventy-seven percent of the initial prescriptions seemed to be adapted to the identified or suspected bacteria, but only 63% adequate to recommendations. CONCLUSION: Almost 2/3rd of the antibiotic prescriptions were adequate to the recommendations. The implementation of standardized and specific protocols should contribute to improve the quality of these prescriptions.

Use of 27 parenteral antimicrobial agents in north of France hospitals.

BACKGROUND: Little data are available on antibiotic (AB) use in French hospitals. METHODS: 1995-2001 annual data on WHO defined daily doses (DDD) and hospitalization days (HD) were collected from volunteer hospitals. Twenty-three AB (amikacin, aztreonam, cefepime, cefotaxime, cefpirome, ceftazidime, ceftriaxone, ciprofloxacin, fosfomycin, fusidic acid, levofloxacin, imipenem, isepamicin, ofloxacin, pefloxacin, piperacillin, piperacillin/tazobactam, quinupristin/dalfopristin, sulbactam, teicoplanin, ticarcillin, ticarcillin-clavulanic acid, vancomycin) and four antifungals (amphotericin B lipid formulations, caspofungin, and fluconazole) were surveyed. Antimicrobial use was expressed as the number of DDD per 1000 HD. RESULTS: Fifty-eight hospitals participated in the 2001 study. AB consumption was higher in hospitals with > 400 acute care beds (214.8 +/- 116 DDD/HD) than in 200-400 beds hospitals (134.2 +/- 39 DDD/HD) or < 200 beds hospitals (104.3 +/- 74 DDD/HD) P = 0.0005. Wide variations in AB choice and volumes were observed among similar sized hospital. Fifteen hospitals, representing one third of the region's acute care beds, provided complete 7-year data. The use of antibacterials increased 23% from 119.9 to 147.2 DDD per 1000 HD. Most of this increase was due to fluoroquinolones (plus 72%; 17.8 vs. 30.6, P = 0.0068), ceftriaxone (plus 90%; 14.4 vs. 27.4; P < 0.0001), and cefepime (plus 264%; 3.4 vs. 12.2%, P = 0.028). The only decreasing class was aminoglycosides (minus 48%; 27.7 vs. 14.5; P = 0.003). CONCLUSIONS: This data confirms the high level of AB consumption in French hospitals.

Effect of different stabilized preparations of peracetic acid on biofilm.

The effect of three stabilized peracetic acid (PAA) preparations (Bioxal M), with or without surfactants, on an Escherichia coli biofilm model was studied. The biofilm was prepared in glass tubes, and was evaluated indirectly using spectrophotometry. The ability of the products to fix or remove the biofilm was determined by their detergent activity (DA). None of the preparations tested fixed the biofilm. The effect of Bioxal M-1 on the biofilm was equivalent to the control (sterile water). Bioxal M-2 and Bioxal M-3 displayed slightly positive DAs. Non-ionic surfactant improved the DA of the products. Regardless of disinfectant activity, PAA agents display different DAs depending on their formulation. This criterion could be used to select the weakest biofilm-fixing agents. Users should therefore be concerned about the efficiency of the cleaning stage of medical devices. When choosing PAA products, non-fixing ability should be considered in addition to antimicrobial activity.

[Standardized incidence ratio: a risk index for catheter-related infection surveillance in intensive care units (REACAT network) in Northern France]. / Ratio standardisé d'incidence: un indice de risque pour la surveillance des infections liées aux cathéters veineux centraux en réanimation adulte (réseau REACAT) dans l'inter-région Nord.

BACKGROUND: Nosocomial infection surveillance is one of the major indicators used to compare health care quality in hospital settings. Wards participating in a network with standardized methods can be compared. We propose a risk index adjusted for catheter-related infection (CRI) specific risk factors in the setting of a CRI surveillance network in intensive care units (ICU): the standardized incidence ratio (SIR). METHODS: All central venous catheters (CVC) inserted for more than 48h were prospectively followed until CVC removal or patient discharge in a yearly 4-month surveillance. Standard clinical and microbiological criteria were used to define colonization and CRI. A logistic regression model, developed on a 3-year pooled database, was used as a predictive model of CRI. Expected number of CRI was calculated and compared with the observed number of CRI to estimate SIR for each year and for each ICU per year. RESULTS: From 2000 to 2003, 108 ICU participated in at least one of the 3 surveillance periods, including 6414 CVC. Overall, 239 CRI were identified (incidence density (ID): 3.6 CRI/1000 CVC-days). At multivariate analysis, duration of CVC placement (1.1 [1.0-1.1]), rank (1.7 [1.1-2.2]) and site of CVC insertion (1.6 [1.2-2.1]), use of CVC for antibiotic therapy (0.5 [0.3-0.7]), organ failure at CVC removal (2.2 [1.5-3.2]), infection at another site at CVC removal ([1.9 [1.4-2.6]) were significantly associated with CRI. During the last period of surveillance, 14 ICU had a DI higher than 5.5 CRI/1000 CVC-days. More CRI than expected were significantly observed in two wards including one which followed less than 20 CVC. CONCLUSION: The REACAT surveillance system assesses a novel and reliable risk index which enables identification of ICU with a higher CRI risk and to focus on prevention.

[Management of aspergillosis in immunocompromised patients. Recommendations of Lille University Hospital--4th version--November 2004]. / Prise en charge diagnostique et thérapeutique des infections à Aspergillus sp. chez le patient immunodéprimé. Recommandations du CHRU de Lille--version 4--novembre 2004.

Invasive aspergillosis is a severe complication in immunocompromised patients. The arrival of new antifungal agents motivated the redaction of guidelines, regularly updated, by a Lille University hospital multidisciplinary task force. These guidelines assess diagnostic and therapeutic issues. The main recommended diagnosis tool is the chest CT scan, ordered at the smallest suspicion and, also, measure of the blood and broncho alveolar lavage fluid galactomannan. Treatment guidelines assess prophylaxis, empirical and documented therapy. Primary prophylaxis is warranted in only two cases, pulmonary graft or stem cell transplant in patients with chronic GVH and receiving corticosteroids. Empirical therapy should use one of the available amphotericin B formulations, chosen according to the patient history. Caspofungin is another choice. Documented therapy, depending on presentation, can be a single drug or a combination. First line therapy for single drug is i.v. voriconazole. Lipid formulations of amphotericin B are another choice. A combination therapy can be used as a first line treatment, for multiple lesions, or as salvage therapy. It must include caspofungin, associated with liposomal amphotericin B or voriconazole. A tight cooperation with thoracic surgeons is recommended.

Antibodies to the nef protein and to nef peptides in HIV-1-infected seronegative individuals.

The silent period that follows infection by the human immunodeficiency virus (HIV-1) and precedes seroconversion remains a problem for the screening of blood supply, and knowledge about the mechanism involved in the maintenance of latency is only fragmentary. Using purified nef recombinant protein and six synthetic nef peptides, antibodies to the product of an HIV-1 regulatory gene, the negative regulatory factor (nef) involved in maintenance of proviral latency, were detected by Western blot and radioimmunoassay techniques in HIV-1-seronegative, viral antigen-negative, and virus culture-negative individuals at risk for HIV infection. This antibody response to nef was correlated in eight individuals with the detection of HIV-1 proviral DNA by oligonucleotide hybridization, following enzymatic amplification of HIV DNA in peripheral blood mononuclear cells. Such latent HIV infections have now been followed for up to 6 or 10 months in five individuals. In addition, retrospective and prospective analysis of HIV-1-seropositive individuals have shown (1) antibodies to nef preceding seroconversion, and (2) the persistence of antibodies to nef and of HIV-1 proviral DNA in a case of spontaneous complete HIV-1 seronegativation. Since DNA amplification cannot be currently considered for routine use, screening for anti-nef antibodies followed by confirmation by DNA amplification could represent a basis for new diagnostic strategies. Beyond their diagnostic implications, these findings, suggesting that regulatory genes of the HIV-1 provirus can be expressed prior to the initiation of virion synthesis, may also be applicable in the design of alternative vaccines against the acquired immunodeficiency syndrome.

Predisposing factors for nosocomial pneumonia in patients receiving mechanical ventilation and requiring tracheotomy.

STUDY OBJECTIVES: To assess the incidence of nosocomial pneumonia (NP) after tracheotomy in an ICU population and to determine NP risk factors during the ICU stay, particularly on the day of tracheotomy. DESIGN: A retrospective study using prospectively collected data. SETTING: A 16-bed multidisciplinary ICU. PATIENTS: One hundred thirty-five patients requiring tracheotomy for mechanical ventilation (MV) weaning. RESULTS: The mean (+/- SD) duration of MV before tracheotomy was 17.8 +/-13.4 days. Thirty-seven cases of NP occurred in 35 patients (25.9%), 8.7+/-7.3 days after the tracheotomy procedure. NP cases were classified as early NP (n = 19) if they occurred within 5 days after the procedure (mean, 2.7+/-1.1 days), and as late NP (n = 18) if they occurred beyond the fifth day (mean, 14.4+/-6.1 days). Multivariate analysis identified the following three independent factors associated with early NP: the presence of positive endotracheal aspirates (EAs) with pathogen levels of > or =10(5) cfu/mL (p = 0.0001); hyperthermia (temperature, > or =38.3 degrees C; p = 0.002) on the day of tracheotomy; and the continuation of sedation beyond 24 h after the tracheotomy (p = 0. 0001). Accountable pathogens of early NP were present in EA on the day of tracheotomy (p = 0.001). Cases of late NP were significantly associated with the duration of sedation before the procedure (p = 0. 002) and with hyperthermia (temperature, > or =38.3 degrees C) on the day of tracheotomy (p = 0.0005). The ICU admitting diagnosis, previous NP, duration of administration of antimicrobial agents and MV before tracheotomy, indication for tracheotomy, PO(2)/fraction of inspired oxygen ratio, and use of steroids on the day of the procedure were not associated with the occurrence of NP. The mortality rate of our population was 33.3%, and NP increased this percentage to 54.3%. CONCLUSIONS: Our results could suggest that tracheotomy should be delayed in mechanically ventilated patients with bronchial colonization and hyperthermia, when sedation cannot be discontinued after the procedure, to prevent occurrence of early NP.

Simplified prediction rule for prognosis of patients with severe community-acquired pneumonia in ICUs.

STUDY OBJECTIVES: To develop a simplified prognostic prediction rule for patients admitted to ICUs for severe community-acquired pneumonia (CAP). SETTING: Six ICUs in the north of France. PATIENTS: Five hundred five patients admitted to ICUs over a 9-year period (from 1987 to 1995) for severe CAP. INTERVENTIONS: Retrospective prognosis analysis and multivariate analysis using a credit scoring technique. MEASUREMENTS: The primary outcome measure was ICU mortality. RESULTS: Among the 505 patients, 472 were eligible for the prognosis study. The ICU mortality rate was 22.9%. Multivariate analysis identified, on the basis of the patient's medical history and initial examination on ICU admission, six independent predictors of mortality: age > or = 40 years, anticipated death within 5 years, nonaspiration pneumonia, chest radiograph involvement > 1 lobe, acute respiratory failure requiring mechanical ventilation, and septic shock. An initial risk score based on these factors classified patients into three risk classes of increasing mortality: 4% in class I, 25% in class II, and 60% in class III. Multivariate analysis of events occurring during ICU stay identified three independent predictors of mortality: hospital-acquired lower respiratory tract superinfections, nonspecific CAP-related complications, and sepsis-related complications. An adjustment risk score based on these factors was essential to accurately predict the final outcome of patients in the initial risk class II. CONCLUSIONS: As an aid to clinicians in stratifying the prognosis of patients with severe CAP, the simplified prediction rule used in this study could be useful for therapeutic decisions and appropriate care.

Community-acquired pneumonia in the intensive care unit: epidemiological and prognosis data in older people.

OBJECTIVES: To compare epidemiological data, etiology, and prognosis of severe community-acquired pneumonia (CAP) in the intensive care unit (ICU) according to age (< or > or = 65 years) and to determine prognostic factors of CAP in older people. DESIGN: A retrospective (1987-1992) and prospective (1993-95) multicenter study. SETTING: Six ICUs in the north of France. PATIENTS: Five hundred five patients admitted to an ICU for severe CAP. MEASUREMENTS: Patient characteristics were compared with regard to age. Prognosis of CAP in older patients was studied by stepwise discriminant analysis. RESULTS: Two hundred seventy-eight patients (55%) were aged 65 years or older. Comparison of epidemiological data between older and younger patients revealed a higher prevalence of women (38% vs 29%), more severe underlying comorbidities (anticipated death within 5 years: 59% vs 26%), and more frequent chronic respiratory insufficiency (48% vs 33%) in the older patients. In this study group, 224 organisms were isolated from 172 patients (62%); those identified most frequently were Gram-negative bacilli (34%), S. pneumoniae (32%), and Staphylococcus sp. (19%). Compared with younger patients, no significant differences in bacteriological data were observed. However, crude and attributable mortality rates were significantly higher in the older patients (33% vs 21% and 30% vs 19%, respectively). Prognosis analysis identified four independent predictors of mortality in the older patients: initial septic shock (relative risk (RR) = 3), sepsis-related complications (RR = 4.3), hospital-acquired lower respiratory tract superinfections (RR = 2), and nonspecific pneumonia-related complications (RR = 2.8). CONCLUSION: The bacterial etiology provides some approaches to empirical therapy for older patients with severe community-acquired pneumonia. In addition, the inappropriateness of withholding intensive care for reasons of age alone is emphasized.

Pharmacokinetics of vancomycin during continuous hemodiafiltration.

OBJECTIVE: To study the pharmacokinetics of vancomycin in three patients with acute renal failure related to multi-organ failure during continuous venovenous hemodiafiltration (CVVHD). DESIGN: Prospective exploratory, open-labelled study. SETTING: Critical Care Unit in a University Medical Centre. PATIENTS: 3 patients exhibiting hemodynamic instability and oligo-anuric acute renal failure requiring extra-renal epuration were included in this study. INTERVENTION: Every patient received 7.5 mg/kg IV vancomycin over 1 h for a documented or suspected nosocomial staphylococcal infection. Serum and dialysate outlets samples were collected before infusion and 1, 3, 6, 12, 18, 24 after the end of infusion. MEASUREMENTS AND RESULTS: Mean age was 58.7 years (range 41-79) and mean SAPS 15.7 (9-23). The mean peak concentrations were 27.3 mg/l (range 15.6-45.6) one hour after the end of infusion. The average remaining vancomycin concentration 24 h after the onset of infusion was 3.6 mg/l (range 2.6-4.5). The mean terminal disposition rate constant and elimination half-life were 0.05 h-1 and 13.9 h respectively. Mean total body clearance was 38.9 +/- 4.3 ml/min and dialysate outlet (DO) clearance 4.2 +/- 1.3 ml/min. The mean volume of distribution was 47.4 +/- 6.4 l. CONCLUSION: CVVHD is effective for vancomycin elimination. In these patients, the elimination half-life is almost constant, involving a following injection of vancomycin 12 h later to achieve effective concentrations.

A five-year study of severe community-acquired pneumonia with emphasis on prognosis in patients admitted to an intensive care unit.

OBJECTIVES: To characterize the epidemiology and to determine the prognosis factors in severe community-acquired pneumonia among patients admitted to an intensive care unit. DESIGN: Retrospective clinical study. SETTING: Intensive Care and Infectious Diseases Unit of a municipal general hospital of Lille University Medical School. PATIENTS: 299 consecutive patients exhibiting severe community-acquired pneumonia. MEASUREMENTS AND RESULTS: On admission to ICU, 149 patients required mechanical ventilation for acute respiratory failure and 44 exhibited septic shock. Pulmonary involvement was bilateral in 71 patients. There were 260 organisms isolated from 197 patients (65.9%), the most frequent being Streptococcus pneumoniae (n = 80), Staphylococcus spp. (n = 57) and Gram-negative bacilli (n = 81). Overall mortality was 28.5% (85 patients). According to univariate analysis, mortality was associated with age over 60 years, anticipated death within 5 years, immunosuppression, shock, mechanical ventilation, bilateral pulmonary involvement, bacteremia, neutrophil count < 3500/mm3, total serum protein level < 45 g/l, serum creatinine > 15 mg/l, non-aspiration pneumonia, ineffective initial therapy and complications. Multivariate analysis selected only 5 factors significantly associated with prognosis: anticipated death within 5 years, shock, bacteremia, non-pneumonia-related complications and ineffective initial therapy. CONCLUSION: The effectiveness of the initial therapy appears to be the most significant prognosis factor and, as the one and only related to the initial medical intervention, suggests a need for permanent optimization of our antimicrobial strategies.

Severe community-acquired pneumonia in ICUs: prospective validation of a prognostic score.

OBJECTIVE: To determine predictors of intensive care unit (ICU) mortality in patients with community-acquired pneumonia (CAP), to develop a pneumonia-specific prognostic index, and to evaluate this index prospectively. DESIGN: Combined retrospective and prospective clinical study over two periods: January 1987-December 1992 and January 1993-December 1994. SETTING: Four medical ICUs in the north of France. PATIENTS: Derivation cohort: 335 patients admitted to one ICU were retrospectively studied to determine prognosis factors and to develop a pneumonia-specific prognostic index. Validation cohort: 125 consecutive patients, admitted to four ICUs, were prospectively enrolled to evaluate this index. RESULTS: In the derivation cohort, 16 predictors of mortality were identified and assigned a value directly proportional to their magnitude in the mortality model: aspiration pneumonia (-0.37), grading of sepsis > or = 11 (-0.2), antimicrobial combination (-0.01), Glasgow score > 12+mechanical ventilation (MV) (+0.09), serum creatinine > or = 15 mg/l (+0.22), chest involvement shown by X-ray > or = 3 lobes (+0.28), shock (+0.29), bacteremia (+0.29), initial MV (+0.29), underlying ultimately or rapidly fatal illness (+0.31), Simplified Acute Physiology Score > or = 12 (+0.49), neutrophil count < or = 3500/ mm3 (+0.52), acute organ system failure score > or = 2 (+0.64), delayed MV (+0.67), immunosuppression (+1.38), and ineffective initial antimicrobial therapy (+1.5). An index was obtained by adding each patient's points. According to a receiver operating characteristic curve, the cut-off value of this index was 2.5. In the validation cohort, an index of > or = 2.5 could predict death with a positive predictive value of 0.92, sensitivity 0.61, and specificity 0.98. CONCLUSION: This index, which performs well in classifying patients at high-risk of death, may help physicians in initial patient care (appropriateness of the initial antimicrobial therapy) and guide future clinical research (analysis and design of therapeutic trials).

Epidemiological features and prognosis of severe community-acquired pneumococcal pneumonia.

OBJECTIVE: To describe risk factors of severe pneumococcal community-acquired pneumonia and to study variables influencing outcome. DESIGN: Retrospective (1987-1992) and prospective (1993-1995) study. SETTING: Three participating ICUs from primary care hospitals. PATIENTS: Five hundred and five patients (mean age: 63 +/- 17 years) with severe community-acquired pneumonia (CAP). Three groups of patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without microbial diagnosis (group 3). MEASUREMENTS AND RESULTS: Admission data and data on the disease's course were recorded. The mean Simplified Acute Physiologic Score (SAPS) was 12.5 +/- 5.4. On admission 288 (57 %) patients were mechanically ventilated (mv) and 82 (16.2 %) required inotropic support. A microbial diagnosis was established for 309 (61.2%) patients. S. pneumoniae was isolated in 137 (27.1%) patients. Severe pneumococcal CAP was independently associated with male sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non-aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001). The overall mortality rate was 27.5 % (29.2 % in group 1). In patients with severe pneumococcal CAP, multivariate analysis showed that leukopenia less than 3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01), sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis. CONCLUSIONS: Few features facilitate the identification of pneumococcal CAP on ICU admission. The prognosis is mostly related to severity of illness (leukopenia, septic shock) while comorbidities do not seem to influence outcome. Sepsis-related disorders, ICU complications and adequate antimicrobial chemotherapy are the major variables affecting the outcome during an ICU stay.

Inhaled NO preadministration modulates local and remote ischemia-reperfusion organ injury in a rat model.

Inhaled nitric oxide (iNO) has been shown to have a protective effect in lung ischemia-reperfusion (I/R)-induced injuries. We studied the role of iNO (10 parts/million for 4 h) administered before I/R. In an isolated perfused lung preparation, iNO decreased the extravascular albumin accumulation from 2,059 +/- 522 to 615 +/- 105 microl and prevented the increase in lung wet-to-dry weight ratio. To study the mechanisms of this prevention, we evaluated the role of nitric oxide (NO) transport and lung exposure with matched experiments by using either lungs or blood of animals exposed to iNO and blood or lungs of naive animals. iNO-exposed blood with naive lungs did not limit the extravascular albumin accumulation (2,561 +/- 397 microl), but iNO-exposed lungs showed a leak not significantly different from the group in which both lungs and blood were iNO exposed (855 +/- 224 vs. 615 +/- 105 microl). An improvement in heart I/R left ventricular developed pressure in the animals exposed to iNO showed that blood-transported NO was, however, sufficient to trigger remote organ endothelium and reduce the consequences of a delayed injury. In conclusion, preventive iNO reduces the consequences of lung I/R injuries by a mechanism based on tissue or endothelium triggering.

Fluorescein-labeled dextran concentration is increased in BAL fluid after ANTU-induced edema in rats.

Several methodologies have been developed to assess alveolocapillary membrane permeability in acute lung injury. The purpose of this study was to determine the reliability of FITC-dextran compared with radioactive tracers to assess lung permeability alterations. After intraperitoneal administration of alpha-naphthylthiourea (ANTU, 50 mg/kg) or DMSO-ANTU vehicle, the animals were euthanized and their lungs were studied in an isolated-lung preparation. FITC-dextran or radiolabeled tracers were added to the perfusate. At 2 h the bronchoalveolar lavage (BAL) fluid from the ANTU group showed a significantly greater amount of fluorescence in the supernatant after centrifugation of BAL fluid compared with the DMSO group. Consistent results were observed with the radioactive tracers: there was an increase in extravascular albumin space and extravascular lung water compared with the control group. No cleavage of the FITC from the dextran molecule was evident by chromatography comparing samples recovered from the BAL fluid to the pure FITC-dextran molecule. In conclusion, measurement of FITC-dextran in the supernatant of BAL fluid after intravascular administration is a reliable method of assessing lung permeability changes in vivo and ex vivo.

Effect of hospital-acquired ventilator-associated pneumonia on mortality of severe community-acquired pneumonia.

PURPOSE: The purpose of this article is to evaluate, using two pairwise case-control studies, attributable mortality linked to hospital-acquired ventilator-associated pneumonia (HA-VAP) complicating the intensive care unit (ICU) stay of patients exhibiting severe community-acquired pneumonia (CAP). MATERIALS AND METHODS: Over an 11-year period, 498 patients with severe CAP were collected. Among them, 43 exhibited HA-VAP. In a first case-control study, these patients were matched with control on the basis of six confounding variables known to be general ICU prognosis factors. In a second case-control study, six variables specifically linked to CAP prognosis were used for matching. RESULTS: In the two case-control studies, each case patient was matched with one control patient. In the first analysis, success of matching was achieved in 198 of 258 (77%) variables used for matching. In the second analysis, matching was successful for 242 of 258 (94%) confounding variables used. Eighteen patients died, compared with, respectively, 6 (P = .003) and 7 (P = .01) controls. Attributable mortality of HA-VAP was similar in the two pairwise analyses, respectively, 28% (risk ratio = 3.0; 95% confidence interval, 1.32 to 6.82) and 26% (risk ratio = 2.57; 95% confidence interval, 1.2 to 5.52). CONCLUSION: When confounding factors were controlled, HA-VAP appeared to increase mortality of severe CAP requiring ICU admission.

Mortality due to ventilator-associated pneumonia: impact of medical versus surgical ICU admittance status.

PURPOSE: The purpose of this study was to compare the prognosis of medical versus surgical patients developing ventilator-associated pneumonia (VAP). MATERIALS AND METHODS: An observational cohort study included 125 consecutive patients exhibiting VAP. Incidence of death occurred at two different times: during intensive care unit (ICU) stay and during hospital stay. RESULTS: Eighty-seven patients were included in the medical group and 38 in the surgical group. On ICU admission and at the time of VAP onset, most collected data, such as demographic parameters, severity of underlying diseases, and current illness, risk factors forVAP development andVAP characteristics were similar in the two groups. Mortality rates during ICU and hospital stays were not significantly different in medical (49%, 56%) and surgical (55%, 61%) groups. In multivariate logistic regression model adjusting for main factors of VAP mortality, surgical admittance status demonstrated no significant impact on mortality assessed during ICU stay (AOR = 1.6; 0.6 - 4.3 CI) and during hospital stay (AOR = 1.6; 0.6 - 4.2 CI). CONCLUSIONS: In this series, after adjustment for mortality confounding factors, medical versus surgical admittance status was not a significant determinant of VAP mortality.

Pulmonary stress injury within physiological ranges of airway and vascular pressures.

PURPOSE: The aim of this study was to assess the respective role of a small elevation in pulmonary capillary pressure, airway pressure, or both on alveolar capillary barrier permeability in an isolated perfused rat lung model. MATERIALS AND METHODS: Four groups were studied with low or high airway pressure (LA: 10 mL/kg (tidal volume); HA: 20 mL/kg), low or high pulmonary artery pressure (LP: 9 mm Hg; HP: 12 mm Hg): LALP, HALP, LAHP, and HAHP. The lungs were ventilated and perfused ex vivo for 30 minutes. Quantification of fluorescein isothiocyanate-labeled (FITC) dextran in bronchoalveolar lavage (BAL) fluid and radiolabeled tracers assessed alveolar capillary barrier permeability. RESULTS: BALF FITC-dextran was similar in the three groups with either one or two low-pressure parameters (LALP, LAHP, HALP), but high amounts were found in the HAHP group (375.2 x 10(-6) mg/mL v, respectively, 21.4, 26.2, and 30 x 10(-6) mg/mL, P = .0001). These results were consistent with the albumin space and extravascular lung water: higher values only in the HAHP group statistically different from the other groups (P < .002). Interalveolar pore examined with scanning electron microscopy showed an increase in diameters between LALP and HAHP (P < .0001). CONCLUSIONS: We can conclude that elevation of either the pulmonary artery pressure from 8 to 11 mm Hg or the alveolar pressure from 10 to 15 mm Hg alone does not change the permeability of the alveolar capillary membrane; however, there is an additive effect of these pressures.

The role of aminoglycosides in modern therapy.

Aminoglycosides remain a mainstay of antimicrobial therapy, especially for treatment of serious Gram-negative infections. Aminoglycosides represent cornerstone of antibiotic combination therapy and, despite their well-documented toxicity, continue to be used because of their excellent bactericidal efficacy and their limited tendency towards the development of resistance during therapy. Various factors, particularly their concentration-dependent bactericidal activity and prolonged post-antibiotic effect, indicate that aminoglycosides can be given effectively in a once-daily dosing regimen. Once-daily dosing has also been shown to reduce toxicity in animal studies. Although once-daily administration of amino-glycosides also has a number of practical advantages, questions remain concerning the indications that should be treated, the optimal peak and trough serum concentrations that should be attained, and the requirement for an initial loading dose. The present article examines the role of aminoglycosides in the treatment of serious infections and reviews the evidence presently available to answer questions on their appropriate clinical use.