Showing papers in "Seminars in Respiratory and Critical Care Medicine in 2000"

Chronic thromboembolic pulmonary hypertension.

Abstract: The last 4 decades have witnessed dramatic changes in the treatment of patients with pulmonary hypertension. And with the advances in cardiothoracic surgical techniques, selected patients with chronic thromboembolic pulmonary hypertension (CTEPH) are afforded a surgical remedy for their disease. In the vast majority of these patients, surgical endarterectomy of chronic thromboemboli from the pulmonary vascular bed effectively treats even severe pulmonary hypertension, and as a result, the debilitating symptoms of right heart dysfunction. This article reviews the natural history of chronic thromboembolic disease and outline a suggested diagnostic approach to determine whether a patient with chronic thromboembolic disease might be an appropriate surgical candidate. Pulmonary thromboendarterectomy surgery, and the growing information on the use of pharmacotherapy in inoperable CTEPH, are also reviewed.

Antimicrobial Resistance with Streptococcus Pneumoniae in the United States

Abstract: Among antimicrobial agents that have consistently been efficacious in treating infections due to specific bacteria over extended periods of time, there are few better examples than Streptococcus pneumoniae and penicillin. Until recently in the United States (U.S.), this combination had remained nearly uniformly effective. The sole issue mitigating for or against use of penicillin (or ampicillin) in the management of systemic pneumococcal infections, or oral ampicillin (or amoxicillin) in treating localized, nonlife-threatening pneumococcal infections, was the penicillin allergy status of the patient. In the nonallergic patient, penicillin or its congeners, have been the drugs of choice largely because resistance to these agents remained uncommon. All of that changed dramatically in the U.S. during the early part of the decade of the 1990s with the emergence of high rates of antimicrobial resistance with S. pneumoniae, and concomitantly, the recognition of diminished efficacy when certain other antimicrobials were used to treat pneumococcal infections. The intent of this discussion is to address a variety of specific issues that pertain to the problem of antimicrobial resistance with S. pneumoniae. The format chosen is a selection of the most asked questions regarding S. pneumoniae and antimicrobial resistance, and then answers are provided.

Legionella as a Cause of Severe Pneumonia

Abstract: Legionella pneumophila has been found to be a common cause of community- acquired pneumonia in patients who required intensive care unit (ICU) admission. In many studies, the clinical manifestations for Legionnaires' disease were more severe and the mortality was higher when compared with pneumonias of other etiology. However, this may be due to delay in diagnosis and suboptimal antibiotic therapy, rather than enhanced virulence of L. pneumophila. A syndromic approach using high fever, diarrhea, mental sta- tus changes, hyponatremia, etc., may be useful in suggesting the correct diagnosis in pa- tients with severe pneumonia, but this remains to be validated. The availability of Le- gionella diagnostic microbiology testing in-house (rather than being sent to an outside reference laboratory) maximizes the ability to correctly diagnose Legionnaires' disease. All patients with community-acquired pneumonia admitted to an ICU should undergo Le- gionella testing using the urinary antigen and culture on selective media. Moreover, we recommend routine cultures of the hospital water supply once a year (regardless of whether a case of nosocomial Legionnaires' disease has ever been diagnosed). If Legionella is found in the water supply, all patients with nosocomial pneumonia should undergo di- agnostic tests for Legionella; empiric anti-Legionella antibiotics should be administered pending definitive diagnosis.

Role of bronchoscopy in lung cancer.

Abstract: Advancements in technology and experience have pushed forth the bronchoscope's increasing role in the struggle against lung cancer. The bronchoscope is useful in the following situations: diagnosis, staging, treatment of endobronchial lesions for palliation or cure, early detection of lung cancer, and research. In this article, we provide a concise overview of several endoscopic modalities (i.e., transbronchial needle aspiration, laser photoresection, photodynamic therapy, electrocautery, cryotherapy, brachytherapy, stents, autofluorescence bronchoscopy, and gene therapy). Basic principles, technique, indications, outcome data, and associated complications of each modality are discussed.

Aerosol therapy in mechanically ventilated patients : Recent advances and new techniques

Abstract: Therapeutic aerosols are commonly used in mechanically ventilated patients, yet information regarding their efficacy and optimal technique of administration has been limited. The advantages of aerosol therapy include a smaller dose, efficacy comparable with that observed with systemic administration of the drug, and a rapid onset of action. Inhaled drugs are delivered directly to the respiratory tract, their systemic absorption is limited, and systemic side effects are minimized. Inhaled bronchodilators are routinely used with mechanically ventilated patients in the intensive care unit, but a variety of drugs ranging from antibiotics to surfactants has been administered. Nebulizers and metered-dose inhalers (MDIs) are commonly used aerosol generators because they produce respirable particles with a mass median aerodynamic diameter (MMAD) between 1 and 5 mum. Due to the limitation of available formulations, MDIs are chiefly used to deliver bronchodilators and steroids, whereas nebulizers have greater versatility and can be used to administer bronchodilators, antibiotics, surfactant, mucokinetic agents, and other drugs. The delivery of inhaled drugs in mechanically ventilated patients differs from that in ambulatory patients in several respects. Until recently, the consensus of opinion was that the efficiency of aerosol delivery to the lower respiratory tract in mechanically ventilated patients was much lower that that in ambulatory patients. Data suggest that this might be overly pessimistic and that the endotracheal tube may actually facilitate greater aerosol delivery compared with the normal airway when a variety of variables effecting aerosol delivery during mechanical ventilation are optimized.

Antibiotic side effects.

Abstract: There is recent enhanced interest in the potential of medication to produce serious toxicity, and the television media have focused on the serious side effects and drug-drug interactions caused by antibiotics. In fact, a recent hospital study noted that drug-related toxicity was one of the most common causes of death for hospitalized patients. Antibiotic-induced adverse events contribute to host injury diagnostic confusion and excessive medical costs. In addition, however, a "spin-off'' of antibiotic-induced adverse events is the emergence and dissemination of drug-resistant organisms. This chapter will describe the adverse events and drug-drug interactions produced by those antibiotics that are most commonly prescribed to patients to prevent or treat respiratory tract infections. An effort will also be made to focus on those unique settings (the patient with renal insufficiency, the patient receiving immunosuppressive medication, the pregnant patient, the elderly patient, and the HIV-infected patient who is a candidate for primary or secondary prophylaxis for Pneumocystis carinii) that require a knowledge of antibiotic-induced adverse events.

Bronchiolitis obliterans organizing pneumonia.

Abstract: Bronchiolitis obliterans with organizing pneumonia (BOOP) is a pathological syndrome common to a variety of pulmonary inflammatory disorders. It is defined by the presence of buds of granulation tissue consisting of fibroblasts and collagen within the lumen of the distal airspaces. BOOP may be secondary to lung injury resulting especially from infection or drug toxicity or may develop in the context of connective tissue diseases or after lung or bone marrow transplantation. BOOP may also be idiopathic (and then preferentially called cryptogenic organizing pneumonia) and then is the hallmark of a distinct clinicoradiological syndrome of subacute pneumonia, with typical alveolar patchy and often migratory pulmonary opacities on imaging. Other imaging presentations consist of diffuse infiltrative opacities or focal pneumonia. Improvement with corticosteroids is usually spectacular, but relapses are common after stopping or while reducing treatment.

New antibiotics in pulmonary and critical care medicine: focus on advanced generation quinolones and cephalosporins.

Abstract: The primary goal in the treatment of respiratory tract infections is to provide the best possible clinical outcome for the patients. In order for this to occur, one must consider and synthesize a tremendous amount of data, much of it changing continually. Important considerations include the pharmacokinetics of the selected agent, its microbiological potency when used alone and in combination with various other agents, and the susceptibilities of the target organisms. Gram-negative bacilli remain among the most frequent cause of bacterial infection in the intensive care unit and in debilitated populations. They also have the ability to resist the best therapies. Among the topics to be discussed here are the important pharmacodynamic concepts and their role in the determination of clinical efficacy, the newer quinolone agents, newly emerging mechanisms of resistance, and recent countermeasures that have been added to the therapeutic armamentarium. In addition, specific strategies designed to combat current resistance trends supported by several recent publications will be reviewed.

Epidemiology of lung cancer with special reference to genetics, bioassays, women, and developing countries.

Abstract: The twentieth century may be looked back upon as the century of lung cancer. At the beginning of the century lung cancer was quite rare, but this century the rates have increased approximately 10-fold and it is the second most common type of cancer and has become the leading cause of death due to cancer in the United States. The rate of lung cancer among U.S. women continues to rise, in contrast rates in U.S. men have been declining since about 1990. Cigarette smoking accounts for 85-90% of lung cancer deaths in the United States. However, only 10-15% of smokers eventually develop lung cancer. In the past 25 years, since the U.S. Surgeon General's ground breaking report in 1964, overall smoking rates have been declining, but smoking still remains a significant behavior. More troubling, the rates of smoking continue to increase in many parts of the world. Advances in molecular biology and early diagnosis have increased the understanding of lung cancer etiology and may be effective in uncovering more efficient detection and treatment regimens. These advances will hopefully make lung cancer as uncommon at the end of the twenty-first century, as it was at the beginning of the twentieth century.

The role of the D-dimer in the diagnosis of venous thromboembolism.

Abstract: Classic enzyme-linked immunosorbent assay (ELISA) D-dimer assays are sensitive in screening for thromboembolic disease; however, they are cumbersome and time consuming to perform, which limits their routine use. Latex agglutination assays are easier to perform, but they are not as sensitive as the ELISA assays. New D-dimer assays incorporating novel technologies can be performed rapidly with a sensitivity approaching that of classic ELISA assays. D-dimer assays are uniformly sensitive in detecting thromboembolic disease in different patient populations; however, low specificity limits the clinical utility of D-dimer measurements in medical inpatients and postoperative patients. Increasingly, these measurements are being incorporated into diagnostic algorithms for venous thromboembolism and are reducing the need for invasive diagnostic studies.

Screening for lung cancer in high-risk groups: current status of low-dose spiral CT scanning and sputum markers.

Abstract: Lung cancer is the number one cause of death from cancer in the United States. Currently, there is no official recommendation to screen for lung cancer even in high-risk populations. Accordingly, we wait for patients to present with symptoms. Only 15-20% of patients are stage I lung cancer at diagnosis. Past screening trials with chest roentgenogram and sputum cytology did not show a reduction of lung cancer mortality in the screened population. Since the completion of those trials in the early 1980s we have learned that the chest X ray is not sensitive at detecting lesions <2 cm in size, and patients with chronic obstructive pulmonary disease (COPD) have a 4- to 6-fold increased risk of lung cancer independent of their smoking history. Recent trials with spiral computed tomography (CT) scan screening have detected 80-85% of lung cancers while they are stage I. The problems related to spiral CT screening are the cost and the frequent detection of benign lesions. Algorithms are being developed to try and prevent unnecessary biopsies and/or surgery. Sputum cytology is currently the only clinically approved sputum test for detecting lung cancer. However, in patients with moderate dysplasia of cytology, the LIFE autofluorescence bronchoscopy system may yield an increased sensitivity of detecting precancerous or cancerous lesions. More studies are needed before the LIFE system can be adopted as a standard clinical tool. Currently, investigators are evaluating the sputum for early lung cancer detection markers. The marker that is the most developed is the monoclonal antibody to the heterogeneous nuclear ribonucleoprotein A2/B1 on the sputum epithelial cell surface. Encouraging preliminary results have been reported and trials are ongoing. The future looks bright for the field of lung cancer screening.

The diagnostic approach to deep venous thrombosis.

Abstract: Accurate diagnosis of deep vein thrombosis is important because untreated deep vein thrombosis can cause death or permanent impairment and because effective treatments are available. The approach to the diagnosis of deep vein thrombosis varies because of differences in local resources and expertise. Duplex ultrasonography with venous compression is the preferred initial test for the majority of outpatients who present with symptoms and signs that suggest acute deep vein thrombosis. Clinical outcome studies have shown the safety of withholding anticoagulants when two compression ultrasonography examinations are negative over a 5- to 7-day period. Alternative strategies, for example, combining clinical scores and D-dimer with compression ultrasonography, may also prove effective. In unusual circumstances, venography or even magnetic resonance imaging may be necessary.

The clinical spectrum of stenotrophomonas (xanthomonas) maltophilia respiratory infection.

Abstract: During a 15-month retrospective clinical study in an academic referral-based cancer center, 26 patients with S. maltophilia respiratory tract infections were identified (which were associated with bacteremia in 13 patients). Five of these 26 patients had previously undescribed sinopulmonary involvement. The infections were typically nosocomial. Nine patients with solid tumors had malignant involvement of the respiratory tract (five with obstruction). In two patients, the infection co-existed with pulmonary aspergillosis. Fifteen patients (58%) died of the infection. The factors that correlated with a poor outcome included bacteremic pneumonia, persistent neutropenia, presence of obstruction, development of septic shock or multiple organ dysfunction, and delay in institution of appropriate antibiotic therapy. In multivariate analysis, only septic shock and delayed therapy remained significant. Trimethoprim-sulfamethoxazole and/or ticarcillin-clavulanate were most commonly associated with a favorable outcome.

Problem pulmonary pathogens: Pseudomonas aeruinosa.

Abstract: Pseudomonas aeruginosa is a common and highly lethal agent of nosocomial pneumonia, especially among patients receiving mechanical ventilation. It is widespread in the environment and commonly recovered from water in nature and in hospital settings. P. aeruginosa is endowed with a formidable array of virulence factors that facilitate attachment to host cells, tissue invasion, and systemic disease. It is intrinsically resistant to many commonly used antibiotics due to a complex variety of mechanisms that we will briefly review. Recent advances in the understanding of the molecular biology of this organism have shed considerable light on its ability to form biofilms, which facilitate adherence especially in cystic fibrosis patients, and confer resistance to clearance by host immune mechanisms and antimicrobial killing. Treatment studies have demonstrated a significant risk of emergence of resistance during therapy with a variety of agents. Several studies suggest that two drugs are better than one for therapy of serious infections, although dual therapy does not always prevent emergence of resistant strains.

Hereditary and acquired thrombophilia.

Abstract: During the past decade knowledge about the etiology of venous thromboembolism has increased tremendously. Inherited and acquired risk factors for venous thromboembolism are common in patients as well as in the general population. Whether the presence of most of these risk factors has consequences for the management of symptomatic and asymptomatic individuals is not fully clear at present. Therefore, while searching for new thrombophilic defects, it is crucial to determine the absolute risk for (recurrent) venous thromboembolism as well as other clinical manifestations in carriers. However, tentative guidelines for managing patients and their families are given in this review.

Economic issues in lung cancer.

Abstract: The purpose of this study is to review the economics of lung cancer management. The economic literature that relates to the diagnosis, treatment, and palliation of lung cancer as well as the pertinent methodological literature were reviewed. Lung cancer treatment is moderately expensive. The overall cost to society is significant given its high incidence. The cost of staging lung cancer can be minimized through the judicious use of diagnostic and staging procedures. The cost-effectiveness of combined modality therapy and palliative chemotherapy for lung cancer appears reasonable when compared with commonly accepted medical interventions. Based on this review, current approaches to lung cancer diagnosis and treatment are, for the most part, cost-effective. Reasons for inconsistent practice patterns in the management of lung cancer in the medical community should be further explored.

Venous thromboembolism: risk factors and prophylaxis.

Abstract: Venous thromboembolism is a common disease in the community and the most frequent preventable cause of hospital death. Acquired and inherited risk factors for thrombosis have been extensively studied over the past two decades. These factors and the clinical setting allow the stratification of most hospitalized patients into low-, moderate-, and high-risk groups. For patients in the moderate- and high-risk categories, routine thromboprophylaxis can decrease the morbidity and mortality from thromboembolic complications as well as reduce patient care expenditures. Low-dose heparin is generally the most appropriate prophylaxis for moderate-risk patients, and either low molecular weight heparin or adjusted-dose warfarin is generally the most appropriate for high-risk patients.

Antibiotic resistance: a historical perspective.

Abstract: Antibiotic resistance is an increasing problem worldwide. Much of the antibiotic resistance occurs among community-acquired and nosocomial pulmonary pathogens. Antibiotic resistance may be classified as relative or absolute, which has important therapeutic implications. Considerable misunderstanding exists with regard to the factors that are responsible for antibiotic resistance. Misuse and overuse of antibiotics should be avoided; however, high volume of antibiotic use alone does not result in resistance. Antimicrobial resistance is agent specific and not related to antibiotic class. The antibiotics associated with a high resistance potential include ampicillin, cefamandole, ceftazidime, imipenem, ciprofloxacin, and vancomycin. The use of these antibiotics should be restricted to prevent generalized resistance problems. The substitution on the formulary of ;;vacuum cleaner'' antibiotics, along with effective infection control measures, can eliminate resistance problems in institutions. The key to controlling antibiotic resistance is to selectively use antibiotics with a low resistance potential and restrict those with a high resistance potential.

Spiral CT for pulmonary embolism.

Abstract: Radiologic imaging for pulmonary embolism has been problematic. Ventilation perfusion scanning is frequently inconclusive; pulmonary angiography has been traditionally underused. Now spiral computed tomographic (CT) angiography provides a readily available, noninvasive test for pulmonary embolism. The accuracy of this examination is exceedingly high, so it should become the first-line test for pulmonary embolism. Recent investigations reveal a high negative predictive value for spiral CT, further proving its value. In addition, spiral CT provides an alternative diagnosis in a high percentage of patients. This article reviews current literature regarding the sensitivity, specificity, reliability, consistency, and cost-effectiveness of spiral CT.

Tracheal gas insufflation.

Abstract: Tracheal gas insufflation (TGI) is an adjunct to mechanical ventilation that reduces CO (2) present in the anatomic deadspace. This is accomplished by flowing fresh gas (typically 6-10 lpm) directly into the trachea via a catheter placed into the endotracheal tube positioned at the distal end or by an embedded catheter in the wall of a specially designed endotracheal tube. This is thought to improve gas mixing because of the turbulent flow created at the tip of the catheter. There are two methods of gas flow delivery and cycling. Gas flow may be delivered directly toward the carina or in a reverse flow fashion. Cycling of TGI flow may be just during exhalation or during both inhalation and exhalation. A system integrated into the monitoring and controls of a mechanical ventilator could eventually prove the safest and most effective. However, currently there are no FDA-approved devices for TGI administration. It is critical to monitor the adverse effects (triggering, auto-PEEP [positive end expiratory pressure], air trapping, and patient comfort) created by the additional flow introduced into the ventilator circuit, while balancing the CO (2) clearance. There are limited data, mostly from animal studies. However, the trials done in both animal and humans are promising with regard to effective CO (2) elimination and avoidance of unacceptably high peak airway pressures. Available equipment has limited studies with infants. Even within the adult population, much work needs to be done to determine the optimal catheter position, the most appropriate TGI flow characteristics, and improve the safety of TGI.

Chlamydia pneumoniae pneumonia.

Abstract: Chlamydia pneumoniae is a common cause of community-acquired pneumonia. At present there is no "gold'' standard for diagnosis and there is no easily accessible means of rapid diagnosis available. The best indication of acute C. pneumoniae infection is a fourfold rise in antibody titer, accompanying a positive polymerase chain reaction or culture. C. pneumoniae is usually associated with nonsevere clinical manifestations but the features will vary depending upon the occurrence as primary or reinfection syndrome, the presence of co-pathogens, or the existence of co-morbid conditions. C. pneumoniae has been described as a cause of severe disease requiring intensive care unit admission. Recommendations for therapy of C. pneumoniae pneumonia include macrolides, tetracyclines, or the new fluoroquinolones.

Hantavirus pulmonary syndrome in the Americas: the early years.

Abstract: The initial recognition of hantavirus pulmonary syndrome (HPS) as a new disease associated with a cluster of acute respiratory deaths among American Indians in the southwestern United States in 1993 bears little resemblance to the current understanding of this syndrome. HPS is now recognized as a zoonotic disease that has been endemic throughout the Americas for at least 40 years and that is closely linked to population densities and virus dynamics among a specific subfamily of rodents. The classic disease description has also been markedly broadened to include a spectrum of illness that ranges from asymptomatic infection to fulminate cardiorespiratory failure. Clinical variants with hemorrhagic or prominent renal manifestations have also been recognized. Prevention efforts have been targeted at minimizing peri-domestic contact with rodents and their excreta and improving clinical recognition of infection. This paper describes the pathogenesis underlying the profound cardiorespiratory compromise, person-to-person transmission reported in South America, and viable treatment modalities.

Techniques for automated feedback control of mechanical ventilation.

Abstract: Mechanical ventilators have become more sophisticated with the advent of microprocessor control. Advances in monitoring have also improved our ability to harmonize patient-ventilator interaction. The next obvious step in this technologic progression is to turn over some decision making to the ventilator. In the jargon of today, we are "closing the loop.'' Ventilators have used closed-loop control for simple tasks for the last decade. Newer closed-loop processes include modes that increase or decrease support based on a single-monitored variable. An example is the automated control of pressure support to maintain a deired tidal volume. More sophisticated closed-loop techniques, such as proportional assist ventilation and adaptive support ventilation, not only monitor multiple input variables but also use closed-loop control of several variables. This article reviews the closed-loop ventilation modes currently available to clinicians.

Use of guidelines and risk stratification in acute exacerbations of chronic obstructive pulmonary disease.

Abstract: Guidelines have been developed to simplify the antimicrobial treatment decision for patients with acute exacerbations of chronic obstructive lung disease. Approximately half of these patients will have a demonstrable bacterial infection and antibiotics have been demonstrated to shorten the clinical illness and prevent significant deterioration. Patients can be stratified by the risk of treatment failure with usual first-line antimicrobial agents. Patients presenting with worsening dyspnea, increased sputum volume and purulence should be offered antimicrobial therapy. In the presence of significant impairment of lung function (FEVI 50% predicted), frequent exacerbations, significant comorbidity, malnutrition, chronic corticosteroid administration and long duration of disease, should be treated with more aggressive therapy such as with a fluoroquinolone, amoxicillin-clavulanate, or a second or third generation cephalosporin or second generation macrolide. In the absence of these risk factors, first-line agents such as amoxicillin appear adequate. Patients with chronic suppurative airway disease (mainly bronchiectasis) should be treated with an antipseudomonal fluoroquinolone if P. aeruginosa is identified in pulmonary secretions. More prospective randomized trial are warranted to validate this approach.

Monotherapy of nosocomial pneumonia.

Abstract: Nosocomial pneumonia remains a common problem and is the leading cause of death among patients with nosocomial infection. However, the initial empiric therapy of nosocomial pneumonia is directed at the leading organisms common to all patients, and for many patients monotherapy is adequate for at least 48 hours, at which time the microbiological results of appropriate diagnostic procedures should be known and the treatment can be focused. The currently available antimicrobial agents such as third- and fourth-generation cephalosporins, piperacillin plus tazobactam, carbapenems, and some fluoroquinolones are highly active and bactericidal. They should be used in consideration of current pharmacodynamic knowledge, which will lead to convincing clinical results. Combination of antibiotics is necessary only in specific situations or for the amelioration of special pathogens, such as Pseudomonas aeruginosa, Acinetobacter spp., and against mixed aerobic and anaerobic infections.

Mechanical ventilation strategies for lung protection

Abstract: Robust data suggest that both maximal and tidal overdistension of lung regions can produce both direct lung injury and a release of inflammatory mediators into the circulation. Animal data also suggest that additional injury results from repetitive alveolar recruitment-derecruitment. Ventilator management strategies aimed at limiting maximal distension (and optimising recruitment) are called lung-protective strategies. Because minute ventilation can be compromised by these strategies, gas exchange may suffer in a trade-off for this protection. Recent clinical trial results showing mortality benefits of lung protection, however, provide strong evidence that this trade-off is worthwhile.

The inflammatory response in chronic bronchitis.

Abstract: Chronic bronchitis is diagnosed clinically by a chronic productive cough and is characterized by a variety of pathological changes, including bronchial gland hyperplasia, goblet cell metaplasia, and peribronchiolar fibrosis. As implied by the term ;;bronchitis,'' chronic airway inflammation is typically found in the central airways in patients with persistent cough and mucus hypersecretion. Although the exact pathogenesis of chronic bronchitis remains unclear, bacterial colonization and the resulting inflammatory response are thought to be of central importance. The generation of proinflammatory cytokines and chemotactic stimuli by the airway epithelium likely plays a central role in propagating the inflammatory response in patients with chronic bronchitis. Typically, an inflammatory mononuclear cell infiltrate is found in the airway wall, and the airway lumen is filled with neutrophils and their products. Further insights into the initiating events and underlying mechanisms that result in the clinical syndrome of chronic bronchitis will likely provide novel opportunities for therapeutic interventions.

Advances in infection control: ventilator-associated pneumonia.

Abstract: Mechanically ventilated patients are 6-21 times more likely to develop nosocomial pneumonia. It is estimated that between 6% and 52% of ventilated patients develop ventilator-associated pneumonia (VAP) with attributable mortality of 27-51%. Certain high risk organisms carry higher mortality (e.g., Pseudomonas aeruginosa and Acinetobacter spp.). Aspiration of colonized orodigestive secretions is the commonly recognized route of infection, whereas inhalation of contaminated aerosol hematogenous spread and direct infection are less common. Gram-negative pathogens are responsible for 40-60% of VAP, whereas gram-positive pathogens cause 15-20%, and it is commonly polymicrobial. Diagnosis remains difficult, and studies showed that early appropriate treatment can improve patient outcome. Better understanding of the pathogenesis and risk factors is important for implementing more effective infection control measures. Clinical trials evaluating outcome will help in assessing current and future preventive and therapeutic measures.

High-frequency ventilation.

Abstract: High-frequency ventilation (HFV) provides respiratory gas exchange using positive airway pressure-driven tidal breaths that are often smaller than anatomic dead space and breathing frequencies several times faster than normal. Gas transport with HFV involves nonconvective mechanisms such as Taylor dispersion, coaxial flow, and augmented diffusion. Devices to deliver HFV include the jet (an airway injector delivers jet pulses) and the oscillator (a piston oscillates a bias flow of fresh gas). The conceptual advantage to HFV is that maximal airway pressures are limited by the small tidal breath and lung recruitment is optimized by the intrinsic positive end expiratory pressure effect. Outcome has been shown to be improved in pediatric patients at risk for volutrauma. Adult outcome data are still lacking.

The antibiotic treatment of severe community-acquired pneumonia admitted to the critical care unit.

Abstract: Community-acquired pneumonias (CAP) are still caused by Streptococcus pneumoniae, Hemophilus influenzae, or Moraxella catarrhalis. Legionella and Chlamydia pneumoniae have been defined as important atypical pathogens causing CAP. Klebsiella causes CAP primarily in patients with chronic alcoholism or in chronic care facilities. Normal hosts do not present with "unusual pathogens'' e.g., Staphylococcus aureus or Pseudomonas aeruginosa. The clinical severity of a bacterial pneumonia has important prognostic implications and predicts admission to intensive care units, duration of therapy, and complications. The factors that determine the severity of a CAP are less related to the pathogen than the underlying cardiopulmonary status of the patient as well as the patient's humoral immunity. Relatively avirulent pathogens may result in severe CAP in patients with diminished/absent splenic function or significant cardiopulmonary disease. A critical concept is to appreciate that the selection of antimicrobial therapy is not dependent on co-morbidities since the antimicrobial therapy is directed against the pathogen and not the co-morbidities. Therefore the treatment of CAP, whether moderate or severe is with the same antibiotic at the same dose. Many antibiotic regimens are equally efficacious in the treatment of CAP. The most cost effective optimal regimen covers both typical and atypical pathogens, e.g., levofloxacin, and is currently the preferred antibiotic approach to moderate or severe CAP in the CCU.