Supporting innovation in health care: A short experience in a dedicated unit of the French Ministry of Public Health.

INTRODUCTION: The Delegation for Innovation in Health Care (DIES) was created by the Ministry of Solidarity and Health to centralize and support innovative health care projects. Following its dissolution, only two and a half years after its creation, the members of this delegation aimed to present the projects, which were submitted and treated by the DIES. METHODS: All potential project leaders were free to explain the objectives of their project to our team. These projects were then classified according to their objective, their type, the medical specialty concerned, the target population and their purpose. The DIES graded the degree of innovation, advised on the need for complementary scientific evaluation and oriented the personnel in charge towards fitting financing structures. RESULTS: Between April 2016 and December 2018, the DIES received 269 potential project leaders, almost exclusively from the national territory of France, focused on diversified medical specialties with a slight predilection for chronic diseases and disabilities. The projects were often at an economically tenuous stage of development. Less than 5% of the projects concerned drug therapy. More than a third involved medical devices, including "surgical" projects (predominately orthopedics), disability compensation methodology, vascular problems and bandages. E-health, the organization of care, and a "non-classifiable" category that included wellness projects each represented 20% of the projects. Almost 80% of these projects had some electronically (e-) based mechanism. Only 15% of all projects had the ambition to meet an unmet or poorly covered need. Only about a third of the project leaders presented a clinical or medico-economic evaluation with sufficiently rigorous methodology to assess the achievement of their objectives. CONCLUSION: Innovative health projects are dominated by the search for improvement in the organization of the health care system and the care pathway with e-connected applications. Evaluation of the vast majority of these projects is very difficult and this situation reinforces the idea that these requests should be centralized to improve support for promoters of innovation.

Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study.

RATIONALE: COVID-19 ARDS could differ from typical forms of the syndrome. OBJECTIVE: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. METHODS: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). MEASUREMENTS AND MAIN RESULTS: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively. CONCLUSIONS: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

Ilio-psoas hematoma in the intensive care unit: a multicentric study.

BACKGROUND: Clinical features and outcomes of patients with spontaneous ilio-psoas hematoma (IPH) in intensive care units (ICUs) are poorly documented. The objectives of this study were to determine epidemiological, clinical, biological and management characteristics of ICU patients with IPH. METHODS: We conducted a retrospective multicentric study in three French ICUs from January 2006 to December 2014. We included IPH diagnosed both at admission and during ICU stay. Surgery and embolization were available 24 h a day for each center, and therapeutic decisions were undertaken after pluridisciplinary discussion. All IPHs were diagnosed using CT scan. RESULTS: During this period, we identified 3.01 cases/1000 admissions. The mortality rate of the 77 included patients was 30 %. In multivariate analysis, we observed that mortality was independently associated with SAPS II (OR 1.1, 95 % CI [1.013-1.195], p = 0.02) and with the presence of hemorrhagic shock (OR 67.1, 95 % CI [2.6-1691], p = 0.01). We found IPH was related to anticoagulation therapy in 56 cases (72 %), with guideline-concordant reversal performed in 33 % of patients. We did not found any association between anticoagulant therapy type and outcome. CONCLUSION: We found IPH is an infrequent disease, with a high mortality rate of 30 %, mostly related to anticoagulation therapy and usually affecting the elderly. Management of anticoagulation-related IPH includes a high rate of no reversal of 38 %.

Daily FOUR score assessment provides accurate prognosis of long-term outcome in out-of-hospital cardiac arrest.

BACKGROUND: The accurate prediction of outcome after out-of-hospital cardiac arrest (OHCA) is of major importance. The recently described Full Outline of UnResponsiveness (FOUR) is well adapted to mechanically ventilated patients and does not depend on verbal response. OBJECTIVE: To evaluate the ability of FOUR assessed by intensivists to accurately predict outcome in OHCA. METHODS: We prospectively identified patients admitted for OHCA with a Glasgow Coma Scale below 8. Neurological assessment was performed daily. Outcome was evaluated at 6 months using Glasgow-Pittsburgh Cerebral Performance Categories (GP-CPC). RESULTS: Eighty-five patients were included. At 6 months, 19 patients (22%) had a favorable outcome, GP-CPC 1-2, and 66 (78%) had an unfavorable outcome, GP-CPC 3-5. Compared to both brainstem responses at day 3 and evolution of Glasgow Coma Scale, evolution of FOUR score over the three first days was able to predict unfavorable outcome more precisely. Thus, absence of improvement or worsening from day 1 to day 3 of FOUR had 0.88 (0.79-0.97) specificity, 0.71 (0.66-0.76) sensitivity, 0.94 (0.84-1.00) PPV and 0.54 (0.49-0.59) NPV to predict unfavorable outcome. Similarly, the brainstem response of FOUR score at 0 evaluated at day 3 had 0.94 (0.89-0.99) specificity, 0.60 (0.50-0.70) sensitivity, 0.96 (0.92-1.00) PPV and 0.47 (0.37-0.57) NPV to predict unfavorable outcome. CONCLUSION: The absence of improvement or worsening from day 1 to day 3 of FOUR evaluated by intensivists provides an accurate prognosis of poor neurological outcome in OHCA.

Granulocytic myeloid-derived suppressor cells inversely correlate with plasma arginine and overall survival in critically ill patients.

Critically ill patients display a state of immunosuppression that has been attributed in part to decreased plasma arginine concentrations. However, we and other authors have failed to demonstrate a clinical benefit of L-arginine supplementation. We hypothesize that, in these critically ill patients, these low plasma arginine levels may be secondary to the presence of granulocytic myeloid-derived suppressor cells (gMDSC), which express arginase known to convert arginine into nitric oxide (NO) and citrulline. Indeed, in a series of 28 non-surgical critically ill patients, we showed a dramatic increase in gMDSC compared to healthy subjects (P = 0·0002). A significant inverse correlation was observed between arginine levels and gMDSC (P = 0·01). As expected, gMDSC expressed arginase preferentially in these patients. Patients with high gMDSC levels on admission to the medical intensive care unit (MICU) presented an increased risk of death at day 7 after admission (P = 0·02). In contrast, neither plasma arginine levels, monocytic MDSC levels nor neutrophil levels were associated with overall survival at day 7. No relationship was found between body mass index (BMI) or simplified acute physiology score (SAPS) score, sequential organ failure assessment (SOFA) score or gMDSC levels, eliminating a possible bias concerning the direct prognostic role of these cells. As gMDSC exert their immunosuppressive activity via multiple mechanisms [production of prostaglandin E2 (PGE2 ), interleukin (IL)-10, arginase, etc.], it may be more relevant to target these cells, rather than simply supplementing with L-arginine to improve immunosuppression and its clinical consequences observed in critically ill patients.

Comparison of intensive-care-unit-acquired infections and their outcomes among patients over and under 80 years of age.

BACKGROUND: Patients aged >80 years represent a growing population admitted to intensive care units (ICUs). However, little is known about ICU-acquired infection (IAI) in this population, and the rate of invasive procedures is increasing. AIM: To evaluate the frequency and effects of IAI in elderly (≥80 years) and younger patients. METHODS: Retrospective evaluation of consecutive patients hospitalized for three days or more over a three-year period in an 18-bed ICU in an academic medical centre. FINDINGS: Elderly patients represented 18.9% of the study population. At admission, the mean number of organ dysfunctions was similar in elderly and younger patients. The use of invasive procedures was also similar in elderly and younger patients, as follows: invasive mechanical ventilation for more than two days, 67.4% vs 55%; central venous catheterization, 56.9% vs 51.4%; and renal replacement therapy, 17.6% vs 17.8%, respectively. The frequency of IAI was 16.5% in elderly patients and 13.9% in younger patients (P = 0.28), with 20.5 vs 18.9 IAI episodes per 1000 ICU-days, respectively (P = 0.2). A Cox model identified central venous catheterization and invasive mechanical ventilation for more than two days as independent risk factors for IAI. The associations between IAI and prolonged ICU stay, increased nursing workload, and ICU and hospital mortality rates were similar in elderly and younger patients. CONCLUSIONS: The frequency of IAI was similar in elderly and younger patients, as were the associations between IAI and length of ICU stay, nursing workload and ICU mortality in an ICU with a high rate of invasive procedures.

Assessment of five screening strategies for optimal detection of carriers of third-generation cephalosporin-resistant Enterobacteriaceae in intensive care units using daily sampling.

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.

Mediastinitis due to Gram-negative bacteria is associated with increased mortality.

The aim of this study was to describe the features of a large cohort of patients with postoperative mediastinitis, with particular regard to Gram-negative bacteria (GNB), and assess their outcome. This bicentric retrospective cohort included all patients who were hospitalized in the Intensive Care Unit with mediastinitis after cardiac surgery during a 9-year period. Three hundred and nine patients developed a mediastinitis with a mean age of 65 years and a mean standard Euroscore of six points. Ninety-one patients (29.4%) developed a GNB mediastinitis (GNBm). Of the 364 pathogens involved, 103 GNB were identified. GNBm were more frequently polymicrobial (44% versus 3.2%; p <0.001). Being female was the sole independent risk factor of GNBm in multivariate analysis. Initial antimicrobial therapy was significantly more frequently inappropriate with GNBm compared with other microorganisms (24.6% versus 1.9%; p <0.001). Independent risk factors for inappropriateness of initial antimicrobial treatment were GNBm (OR = 8.58, 95%CI 2.53-29.02, p 0.0006), and polymicrobial mediastinitis (OR = 4.52, 95%CI 1.68-12.12, p 0.0028). GNBm were associated with more drainage failure, secondary infection, need for prolonged mechanical ventilation and/or use of vasopressors. Thirty-day hospital mortality was significantly higher with GNBm (31.9 % versus 17.0%; p 0.004). GNBm was identified as an independent risk factor of hospital mortality (OR = 2.31, 95%CI 1.16-4.61, p 0.0179).

Drowning associated pneumonia: a descriptive cohort.

PURPOSE: Pneumonia is the most common infectious complication of drowning. Pneumonia is potentially life threatening and should be treated by effective antibiotic therapy. However the risk factors, microbiological causes, diagnostic approach and appropriate therapy for pneumonia associated with drowning are not well described. The microbiological ecology of the body of water where immersion occurred could be of import. The aim of this study was to report on microorganisms involved in pneumonia associated with drowning and out of hospital cardiac arrest after successful cardiopulmonary resuscitation. Additionally, we retrieved and undertook microbiological analysis on samples of water from our local river. METHODS: This retrospective study included all patients having suffered an out of hospital cardiac arrest due to drowning and admitted to our tertiary care academic hospital between 2002 and 2010. Data concerning bacteriological lung samples (tracheal aspirate or bronchoalveolar lavage) at admission were reported and compared to bacteriological samples obtained from our local river (the river Seine). RESULTS: A total of thirty-seven patients were included in the study. Lung samples were obtained for twenty-one of these patients. Lung samples were positive in nineteen cases, with a high frequency of multi-drug resistant bacteria. Samples from the Seine River found microorganisms similar to those found in drowning associated pneumonia. CONCLUSIONS: Drowning associated pneumonia can be due to multi drug resistant bacteria. When treating drowning associated pneumonia, antibiotics should be effective against bacteria similar to those found in the body of water where immersion occurred.

[Acute respiratory distress syndrome due to Toxocara cati infection]. / Syndrome de détresse respiratoire aiguë secondaire à une infection à Toxocara cati.

Human toxocarosis is a helminthozoonosis due to the migration of toxocara species larvae throughout the human body. Lung manifestations vary and range from asymptomatic infection to severe disease. Dry cough and chest discomfort are the most common respiratory symptoms. Clinical manifestations include a transient form of Loeffler's syndrome or an eosinophilic pneumonia. We report a case of bilateral pneumonia in an 80 year old caucasian man who developed very rapidly an acute respiratory distress syndrome, with a PaO2/FiO2 ratio of 55, requiring mechanical ventilation and adrenergic support. There was an increased eosinophilia in both blood and bronchoalveolar lavage fluid. Positive toxocara serology and the clinical picture confirmed the diagnosis of the "visceral larva migrans" syndrome. Intravenous corticosteroid therapy produced a rapid rise in PaO2/FiO2 before the administration of specific treatment. A few cases of acute pneumonia requiring mechanical ventilation due to toxocara have been published but this is, to our knowledge, is the first reported case of ARDS with multi-organ failure.

Diagnosis and treatment of nosocomial pneumonia in ALI/ARDS patients.

Ventilator-associated pneumonia (VAP) is a common complication of the acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), often leading to the development of sepsis, multiple organ failure, and death. However, the diagnosis of pulmonary infection in patients with ARDS/ALI is often difficult: the systemic signs of infection, such as fever, tachycardia, leukocytosis are nonspecific findings in such patients; a variety of causes other than pneumonia can explain asymmetric consolidation in patients with ARDS and marked asymmetry of radiographic abnormalities has also been reported in patients with uncomplicated ARDS. In 2003, physicians in charge of these patients have to identify patients with true bacterial lung infection, to select appropriate initial antibiotic therapy, to adjust therapy as soon as possible, and to withhold antibiotics in patients without VAP. To do that, a bacteriological strategy based on the use of quantitative cultures of specimen obtained with fibreoptic bronchoscopy performed before initiation or modification of antibiotic treatment seems better than a strategy based on clinical evaluation alone, lowering antibiotic consumption and improving outcome. When bronchoscopy is not available or contraindicated, a nonbronchoscopic strategy or a clinical strategy with reevaluation 3 days after initiation of treatment may be used. Antimicrobial treatment of VAP is a complex issue. Some general principles can be helpful for the selection of initial treatment: knowledge of most frequently identified responsible pathogens and their susceptibility patterns in the unit; prior duration of hospitalisation; previously prescribed antibiotics; information obtained by direct examination of pulmonary secretions; antibacterial activity and pharmacodynamic characteristics of antibiotics that could be used to treat this infection. Appropriateness of initial antimicrobial therapy is probably a major prognostic factor for patients with ventilator-associated pneumonia. Thus, before new antiboitics are administered, reliable pulmonary specimens must be obtained for direct examination and cultures.

[Epidemiology and antibiotic therapy in nosocomial pneumonia]. / Epidémiologie et antibiothérapie des pneumopathies nosocomiales.

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.

Autoantibodies against platelet glycoproteins in critically ill patients with thrombocytopenia.

PURPOSE: The aim of the study was to investigate immunologic causes of thrombocytopenia in critically ill patients, especially causes that were related to platelet-associated IgG antibodies. SUBJECTS AND METHODS: All patients admitted to two intensive care units between May 1 and October 30, 1997, who developed thrombocytopenia (less than 100 x 10(9) platelets/L) were studied prospectively. We measured platelet-associated IgG with a radioimmunoassay using I(125)-labeled polyclonal antihuman IgG. Characterization of platelet-associated IgG was assessed with a monoclonal antibody immobilization of platelet antigen. Circulating immune complexes were also assayed. RESULTS: Of the 61 patients with thrombocytopenia, elevated platelet-associated IgG was found in 18 (30%). Associated antiplatelet autoantibodies (glycoprotein IIb/IIIa) were detected in 4 patients, circulating autoantibodies (glycoprotein Ib/IX) were detected in sera from 2 patients, and circulating immune complexes were detected in 3 patients. The nature of the platelet-associated IgG could not be determined in 10 patients. Elevated platelet-associated IgG was associated with sepsis and previous cardiopulmonary bypass. Thrombocytopenic patients with elevated platelet-associated IgG had a lower nadir platelet count (58 +/- 27 x 10(9)/L vs 74 +/- 24 x 10(9)/L, P = 0.03). CONCLUSION: Elevated platelet-associated IgG, some of which are platelet autoantibodies, is frequent in thrombocytopenic patients with sepsis or after cardiopulmonary bypass.

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.

Treatment of gram-positive nosocomial pneumonia. Prospective randomized comparison of quinupristin/dalfopristin versus vancomycin. Nosocomial Pneumonia Group.

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.

[Duration of treatment of nosocomial pneumonia. What judgement criteria to use?]. / Durée de traitement des pneumopathies nosocomiales. Quels critères de jugement utiliser?

AN UNRESOLVED ISSUE: Inappropriate duration of antibiotic treatment is one of the factors explaining the high mortality of nosocomial pneumonia. There are however few data on the ideal duration of treatment. An improvement in the radiological image is not a good criterion. The right duration would be one that is necessary and sufficient to achieve cure and avoid recurrence and relapse and also one that avoids the drawbacks of prolonged treatment. LIMITATIONS OF CLINICAL CRITERIA: High-grade fever, an alveolar image on the chest x-ray, and a high white cell count are synonymous with bacterial pneumonia in only 40 to 60% of the cases. PRIMARY AND SECONDARY INFECTION: Using reliable microbiological methodology is has been possible to demonstrate that the causal germs of primary infections disappear by day 3 of an adapted treatment but that early secondary infection occurs in 14% of the cases. PROSPECTS FOR PROGRESS: An open multicentric randomized study is being conducted in France to compare 7 day versus 14 day treatment against identified germs (irrespective of the strain isolated) using reliable microbial sampling techniques.