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Hospital-acquired pneumonia (HAP) is the second most common nosocomial infection and the leading cause of mortality attributable to these critical infections [ 1– 3]. Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is now a major cause of HAP [ 4– 6]. Rates of clinical failure in patients with HAP due to MRSA are high [ 7, 8]. Currently, only vancomycin and linezolid are recommended for treatment of HAP due to MRSA [ 9]. Results from recent pneumonia trials with new antibiotics active against MRSA have not been encouraging [ 10– 12]. Therefore, additional antistaphylococcal agents for treatment of HAP are urgently needed. Telavancin is a lipoglycopeptide antibacterial agent exhibiting potent, concentration-dependent bactericidal effects via a dual mechanism of action that combines inhibition of cell wall synthesis and disruption of membrane barrier function [ 13– 15]. In vitro, telavancin is rapidly bactericidal against clinically important gram-positive bacteria, including MRSA, vancomycin-intermediate S. aureus, and penicillin-resistant S. pneumoniae [ 13, 16, 17]. Telavancin penetrates well into the epithelial lining fluid and alveolar macrophages of healthy subjects, achieving concentrations up to 8-fold and 85-fold, respectively, above telavancin's minimum inhibitory concentration (MIC) for 90% (MIC90) of MRSA strains (.5 μg/mL) [ 16, 18]. Unlike daptomycin (a cyclic lipopeptide), telavancin remains active in vitro in the presence of pulmonary surfactant [ 16]. Telavancin is approved in the United States and Canada for the treatment of adult patients with complicated skin and skin-structure infections due to susceptible gram-positive pathogens. The current studies were designed to assess the clinical efficacy and safety of telavancin compared with vancomycin in the treatment of HAP due to gram-positive organisms, with a focus on infections due to MRSA. Partial results of these studies have been previously reported.

The global spread of methicillin-resistant Staphylococcus aureus (MRSA) means it is now a pathogen of worldwide public health concern. Within Latin America, MRSA is highly prevalent, with the proportion of S. aureus isolates that are methicillin-resistant on the rise, yet resources for managing the infection are limited. While several guidelines exist for the treatment of MRSA infections, many are written for the North American or European setting and need adaptation for use in Latin America. In this article, we aim to emphasize the importance of appropriate treatment of MRSA in the healthcare and community settings of Latin America. We present a summary of the available guidelines and antibiotics, and discuss particular considerations for clinicians treating MRSA in Latin America A propagação global de Staphylococcus aureus resistente à meticilina (methicillin-resistant Staphylococcus aureus - MRSA) significa que se trata agora de um patógeno de interesse para a saúde pública mundial. Na América Latina, o MRSA é altamente prevalente, com a proporção de S. aureus resistente à meticilina em ascensão, no entanto os recursos para o tratamento da infecção são limitados. Embora existam várias diretrizes para o tratamento de infecções por MRSA, muitas são elaboradas para a América do Norte ou a Europa e precisam ser adaptadas para sua utilização na América Latina. Neste artigo, procuramos destacar a importância do tratamento adequado do MRSA nas unidades de saúde e na comunidade na América Latina. Apresentamos um resumo das diretrizes e dos antibióticos disponíveis, e discutimos considerações específicas para os médicos que tratam de MRSA na América Latina.

The global spread of methicillin-resistant Staphylococcus aureus (MRSA) means it is now a pathogen of worldwide public health concern. Within Latin America, MRSA is highly prevalent, with the proportion of S. aureus isolates that are methicillin-resistant on the rise, yet resources for managing the infection are limited. While several guidelines exist for the treatment of MRSA infections, many are written for the North American or European setting and need adaptation for use in Latin America. In this article, we aim to emphasize the importance of appropriate treatment of MRSA in the healthcare and community settings of Latin America. We present a summary of the available guidelines and antibiotics, and discuss particular considerations for clinicians treating MRSA in Latin AmericaA propagação global de Staphylococcus aureus resistente à meticilina (methicillin-resistant Staphylococcus aureus - MRSA) significa que se trata agora de um patógeno de interesse para a saúde pública mundial. Na América Latina, o MRSA é altamente prevalente, com a proporção de S. aureus resistente à meticilina em ascensão, no entanto os recursos para o tratamento da infecção são limitados. Embora existam várias diretrizes para o tratamento de infecções por MRSA, muitas são elaboradas para a América do Norte ou a Europa e precisam ser adaptadas para sua utilização na América Latina. Neste artigo, procuramos destacar a importância do tratamento adequado do MRSA nas unidades de saúde e na comunidade na América Latina. Apresentamos um resumo das diretrizes e dos antibióticos disponíveis, e discutimos considerações específicas para os médicos que tratam de MRSA na América Latina.

SummaryThe clinical and economic burden of adult community-acquired pneumonia (CAP) in Latin America is not well known. We conducted a literature review to describe the etiology, incidence, hospitalization, morbidity and mortality, antibiotic resistance, costs associated with care, and the potential benefits of pneumococcal vaccination in the reduction of adult CAP in Latin America. Data that were published during the period from January 1970 through August 2008 were identified via the Web sites and databases of the Pan American Health Organization, Latin American health agencies, and the US National Institutes of Health, National Library of Medicine (MEDLINE). Streptococcus pneumoniae was identified as the most common pathogen, accounting for up to 35% of CAP cases. The mean rate of CAP due to penicillin-resistant S. pneumoniae was 39%. The mortality in Latin America due to lower respiratory tract infections has been reported to be 6%, compared with 4% in developed regions, and CAP was the third most frequent cause of death in adults in 31 Latin American countries in 2001–2003. Although S. pneumoniae caused the majority of CAP, similar to other regions of the world, mortality due to CAP in Latin America was substantially greater than that in developed countries. This review demonstrates the need to facilitate standardized surveillance and reporting systems to monitor the burden of CAP and to implement prevention strategies to decrease the clinical and economic burden of CAP in Latin American adults.

Methicillin-resistant Staphylococcus aureus (MRSA) has become a serious threat to public health worldwide. Ongoing surveillance is essential to support infection control committees and clinicians in the prevention and treatment of infection. However, in Latin America, resources for monitoring the changing epidemiology of MRSA remain limited. In this article, we review the current situation of MRSA in Latin America in order to highlight the need for a more harmonised effort to improve its management. Literature in the PubMed and SciELO databases as well as the website of the Pan American Health Organization were searched for articles and information about the epidemiology of MRSA in Latin America. MRSA is already the leading cause of nosocomial infection in the Latin American region, and the number of reports of community-acquired MRSA infections is also rising. However, the extent of the problem is not fully understood, especially since data tend to come from large hospitals whereas much of the population is served by small community healthcare centres that do not have extensive facilities for performing microbiological surveillance. In conclusion, wider-reaching and co-ordinated programmes to provide regular MRSA surveillance reports are required across the Latin American region.

Objectives To investigate if compared with glycopeptides, antimicrobial therapy (AMT) with linezolid (LZD) improves the outcome in methicillin-resistant Staphylococcus aureus (MRSA) experimental pneumonia in mechanically ventilated piglets. Methods The MRSA minimal inhibitory concentration (MIC) was 0.5 for vancomycin (VAN), 0.25 for teicoplanin (TEI), and 2.0 μg/mL for LZD was inoculated in Largewhite-Landrace piglets divided into five groups. One group (n = 6) did not receive mechanical ventilation (MV) or AMT. Those in the remaining groups received MV and VAN (n = 9), TEI (n = 7), LZD (n = 9), or no AMT (n = 7). Plasma and BAL tumor necrosis factor-α, interleukin-6, and C-reactive protein (CRP) concentrations, postmortem lung pathology, cultures (lung, blood, and BAL) and plasma, epithelial lining fluid (ELF), and lung antibiotic concentrations were evaluated. Measurements and main results All piglets developed severe pneumonia; lung pathology score was lower in those receiving LZD vs those receiving glycopeptides (p = 0.049) or no AMT (p = 0.037). Serum CRP and serum and BAL cytokines increased; there were no differences between the groups. Fourteen died spontaneously at 44.4 ± 16.8 h; the remaining 24 were killed after 72 to 96 h. The concentrations of the antimicrobial agents tested in 15 piglets were higher than the MIC for the three antimicrobial agents in peak and trough plasma, ELF, and lung specimens. Survival at 72 h was higher in the LZD comparing with the no-AMT group. Conclusions Inoculation produced severe MRSA pneumonia. LZD AMT was associated with lower pathology score, better survival, and a trend to better clearance of MRSA, not attributable exclusively to pharmacokinetic or pharmacodynamic reasons.

Animal models are an essential step between "in vitro" testing and clinical studies. Different animal models have been useful for the study of pathophysiology, diagnosis and therapy in ventilator-associated pneumonia (VAP). Aspiration has been studied in dog and cat models and bacteriological diagnosis has been evaluated in baboons. Pigs have been used for studying either spontaneous or induced VAP. Intubated piglets in prone position were administered analgesia and muscle paralysis was induced, and the intubated piglets underwent mechanical ventilation for several days. In this model, spontaneous VAP due to common bacterial pig colonisation develops within a few days. Pneumonia can also be induced by inoculating high concentrations of microorganisms (Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus). Different clinical, physiological, microbiological and pathological parameters of infection have been studied in this model. In addition, administration of antibiotics and inflammatory modulators and their consequences in microbiological eradication and local and systemic inflammation have been evaluated with interesting translational results. Although bronchial inoculation of healthy subjects does not resemble the common pathophysiological mechanisms, the experimental model of ventilator-associated pneumonia induced by the inoculation of high concentrations of microorganisms in mechanically ventilated piglets is useful for the study of the local and systemic responses of lung infection and for the determination of potential measures of prevention or therapeutic modulation.

Acinetobacter spp. and Pseudomonas aeruginosa are common pathogens of ventilator-associated pneumonia (VAP). The presentation and outcome of VAP due to Acinetobacter spp. and P. aeruginosa susceptible to carbapenems (Carb-S; imipenem and/or meropenem) and to colistin only (Col-S) were compared in the present retrospective study in three intensive care units. A total of 61 episodes of VAP caused by Acinetobacter spp. or P. aeruginosa were studied, of which 30 isolates were Carb-S and 31 were Col-S. Demographics, worsening of renal function and mortality were not different. The univariate analysis showed that a later onset and a previous episode of VAP, prior antimicrobial therapy for >10 days and previous therapy with carbapenems during the present admission were more frequent in patients with Col-S strains. On multivariate analysis, prior antimicrobial therapy for >10 days and a previous episode of VAP remained significantly associated with Col-S VAP. Approximately 41% of the infections caused by Col-S isolates, but none of those due to Carb-S isolates, had received prior carbapenem therapy. Colistin-susceptible ventilator-associated pneumonia episodes can be effectively treated using colistin without significant renal dysfunction. This susceptibility pattern could be suspected in patients with a previous ventilator-associated pneumonia episode or prior antibiotic therapy for >10 days preceding the present ventilator-associated pneumonia episode.

Controversy still exists in the international literature regarding the need to use antimicrobials covering atypical pathogens when initially treating hospitalized patients with community-acquired pneumonia (CAP). In different regions of the world, monotherapy with a beta-lactam antimicrobial is common.We sought to correlate the incidence of CAP due to atypical pathogens in different regions of the world with the proportion of patients treated with an atypical regimen in those same regions. In addition, we sought to compare clinical outcomes of patients with CAP treated with and without atypical coverage.A secondary analysis was performed using two comprehensive international databases. World regions were defined as North America (I), Europe (II), Latin America (III), and Asia and Africa (IV). Time to reach clinical stability, length of hospital stay, and mortality were compared between patients treated with and without atypical coverage.The incidence of CAP due to atypical pathogens from 4,337 patients was 22, 28, 21, and 20% in regions I-IV, respectively. The proportion of patients treated with atypical coverage from 2,208 patients was 91, 74, 53, and 10% in regions I-IV, respectively. Patients treated with atypical coverage had decreased time to clinical stability (3.7 vs. 3.2 d, p0.001), decreased length of stay (7.1 vs. 6.1 d, p0.01), decreased total mortality (11.1 vs. 7%, p0.01), and decreased CAP-related mortality (6.4 vs. 3.8%, p = 0.05).The significant global presence of atypical pathogens and the better outcomes associated with antimicrobial regimens with atypical coverage support empiric therapy for all hospitalized patients with CAP with a regimen that covers atypical pathogens.

PURPOSE OF REVIEW: Due to the exponential growth of international exchange, millions of travelers are exposed to respiratory pathogens in the tropics and may return ill. Community-acquired pneumonia is one of the more prevalent infections. RECENT FINDINGS: The acquisition of infections in the tropics, including community-acquired pneumonias, has been described for several centuries. During recent decades some microorganisms have been disclosed as causative of the disease (Legionella pneumophila in 1976 and hantavirus in 1990); other microorganisms are real new pathogens that were not previously demonstrated to have a pathogenic role in humans (e.g. severe acute respiratory syndrome coronavirus producing an outbreak in 2003 and H5N1 avian influenza virus producing an increasing number of human cases over the last few years). SUMMARY: A number of microorganisms may produce pneumonia in people who live or have traveled to tropical zones. History, including geography and epidemiology, physical exam and complementary workout are precious tools for the diagnosis, therapy and prevention. Exposure to microorganisms in tropical areas may show different patterns. A high index of suspicion, detailed investigation of travel, exposure history of the patient, and a basic understanding of the incubation periods and distribution of the various potential pathogens are imperative for the diagnosis.

Alpha-1 antitrypsin (AAT) deficiency represents an under diagnosed disease in which early detection can allow lifestyle changes to prevent or at least postpone the development of impairment. Aim: Determine the prevalence of severe alpha-1 antitrypsin deficiency in candidate patients at the outpatient clinic of a University Hospital. Methods: Candidate patients, according to the SEPAR (Sociedad Espanola de Neumologia y Cirugia Toracica) Guidelines, evaluated at the outpatient clinic of a University Hospital in Argentina were included. Whole blood was obtained by distal finger puncture and the AAT concentration was determined by nephelometry. If the value was below 1.5 mg/dl (equivalent to 83 mg/dl in serum) the genotype of the sample was done through a RT-PCR looking for the mutations of the Z and S genes. Results: 172 patients were included, 129 had COPD (table 1). AAT concentration was determined in 160 samples (12 were inadequate to analyse). AAT deficiency was ruled out in 143 patients (89%). In the remaining 17 samples (11%) we proceeded with the genotyping. One patient (0.625%) was diagnosed with severe AAT deficiency related to the Pi Z allele. Conclusions: The prevalence of severe AAT deficiency in our candidate patients was of 0.625%. Although rare, this condition should be ruled out in some patients. Targeted testing (in selected COPD patients for example) may increase the likelihood of diagnosis.

Rationale & Methods: Advanced age and underlying lung disease are risk factors for CABP morbidity. We evaluated a 4 th generation macrolide antibiotic, Solithromycin (S), vs Moxifloxacin (M) in a global, P3, DB-RCT for CABP of PORT II-IV severity. Outcomes included clinical improvement at 72 hours (early clinical response or ECR) and success at short term follow up visit (SFU), 5-10 days after last dose of study drug. Results: 860 CABP patients from 16 countries were randomized 1:1 to receive oral S or M. Mean age was 58.5 years (S) versus 56.7 years (M). 50.7% of S patients had PORT III/IV CABP (11.3%, PORT IV) vs. 48.6% of M patients (8.8% PORT IV). S was non-inferior to M in ECR and SFU success rates (%) in the ITT population (78.2 vs 77.9 and 84.5 vs 86.6, respectively). Among patients ≥ age 75, ECR and SFU success rates (%) (83.9 vs 69.8 and 85.5 vs 84.1, respectively) favored S. Among patients with history of COPD or asthma, ECR (71.0 vs 67.2) and SFU (91.9 vs 85.9) success rates (%) also favored S. S demonstrated comparable safety to M in the occurrence of adverse events (AEs) (36.6% vs 35.6%), study drug related AEs (10.1% vs 12.5%), Serious Adverse Events (6.6% vs 6.3%) (none attributed to study drug) and deaths (1.4% vs 1.4%). Two episodes of C. difficile diarrhea were detected, both among M recipients. Conclusions: Oral S was non-inferior to oral M for treatment of CABP. Strikingly, S demonstrated greatest efficacy relative to M in the elderly and among patients with history of COPD or asthma. A global P3 CABP trial evaluating IV-to-Oral solithromycin versus moxifloxacin is ongoing.

To study outcome and its predictive factors in cancer patients admitted to the ICU with septic shock, and the implications of neutropenia as a risk factor in this advanced stage of systemic inflammatory response. A prospective consecutive observational cohort study was conducted in 73 adults with cancer and septic shock admitted to the ICU at the Cancer Medical Center associated with the University of Buenos Aires. The mortality rate from septic shock was 53.4% (95%CI 41.9 to 64.8%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission, the mean number of organ dysfunctions on admission or during the ICU stay, liver dysfunction, respiratory dysfunction, and the need for mechanical ventilation were predictive of mortality in a univariate analysis. Neutropenia was not associated with a worse prognosis in terms of mortality (56%) or mean days of ICU stay (6.64 days) in comparison with nonneutropenic patients (52.1% and 6.8 days) in the univariate analysis. In the logistic regression model only the need for mechanical ventilation and liver dysfunction remained independent predictors of mortality. Septic shock among cancer patients admitted to the ICU has a mortality rate similar to that reported for mixed populations, and it is particularly increased when hepatic or respiratory dysfunction develop. Neutropenia on admission does not seem to modify outcome.

La enfermedad de los legionarios es una causa de neumonía adquirida en la comunidad (NAC) reconocida en todo el mundo. En Latinoamérica su incidencia es desconocida. En este estudio se analizó a 9 pacientes con NAC por Legionella pneumophila atendidos entre 1997 y 2001 en el Hospital de Clínicas José de San Martín de la Universidad de Buenos Aires. Se registraron datos de antecedentes, enfermedad actual, contactos, exposición laboral, examen físico, pruebas de laboratorio y uso previo de antibióticos, y se tomó en cuenta la presencia de criterios de gravedad. Nueve pacientes presentaron diagnóstico de NAC por Legionella, ninguno refirió antecedentes de viajes recientes; cuatro de ellos debieron ser internados en unidades de cuidado intensivo. Siete pacientes tenían antecedentes de tabaquismo, 4 tenían EPOC y un paciente linfoma no-Hodgkin. Nuestra casuística corrobora la baja especificidad de la clínica y estudios complementarios para predecir esta etiología. El aislamiento de Legionella es dificultoso, la seroconversión permite el diagnóstico retrospectivo y requiere plazos prolongados y el antígeno urinario aporta un diagnóstico inmediato. Cuando la legionelosis aparece en casos aislados, como ocurriría en Argentina, si no se piensa en esta etiología no se llegará al diagnóstico. Legionella pneumophila es un patógeno de NAC en nuestro medio, debe buscarse mejor, particularmente en pacientes graves, inmunodeprimidos y en fumadores con enfermedad pulmonar obstructiva crónica (EPOC).Legionnaires’ disease is a well recognized cause of community acquired pneumonia (CAP) all around the world. In Latin America its incidence remains unknown. This study analyzed a cohort of 9 patients with CAP due to Legionella pneumophila observed from 1997 to 2001, in the Hospital de Clínicas José de San Martín, University of Buenos Aires. Clinical history included recent illnesses, work exposure, physical exam, prior antibiotic use and severity of illness criteria. None of the 9 patients had a history of recent travels, and 4 of them required admission in intensive care unit (ICU). Seven patients had a cigarette smoking history, four of them also had COPD, and one patient had a non-Hodgkin lymphoma. This study confirms the low specificity of clinical and general laboratory criteria to predict this etiology. Legionella isolation is difficult, and serological testing allows retrospective diagnosis but takes several weeks, while urinary antigen test gives a bed-side diagnosis. When Legionella appears in isolated cases, as happens in Argentina, it should be necessary to have a high index of suspicion to successfully arrive at an etiological diagnosis. Legionella pneumophila is a pathogen causing CAP in our area. A surveillance should be established preferably focused on selected populations including severe CAP, immunocompromised hosts and patients with chronic obstructive pulmonary disease.

We performed a prospective, international, observational study of 844 hospitalized patients with blood cultures positive for Streptococcus pneumoniae. Fifteen percent of isolates had in vitro intermediate susceptibility to penicillin (minimum inhibitory concentration [MIC], 0.12-1 microg/mL), and 9.6% of isolates were resistant (MIC, >or=2 microg/mL). Age, severity of illness, and underlying disease with immunosuppression were significantly associated with mortality; penicillin resistance was not a risk factor for mortality. The impact of concordant antibiotic therapy (i.e., receipt of a single antibiotic with in vitro activity against S. pneumoniae) versus discordant therapy (inactive in vitro) on mortality was assessed at 14 days. Discordant therapy with penicillins, cefotaxime, and ceftriaxone (but not cefuroxime) did not result in a higher mortality rate. Similarly, time required for defervescence and frequency of suppurative complications were not associated with concordance of beta-lactam antibiotic therapy. beta-Lactam antibiotics should still be useful for treatment of pneumococcal infections that do not involve cerebrospinal fluid, regardless of in vitro susceptibility, as determined by current NCCLS breakpoints.

Background . Assessment of surgical risk in patients undergoing pulmonary resection is a fundamental goal for thoracic surgeons. Usually used risk indices do not predict the individual outcome. Neural networks (NN) are artificial intelligence software models that have been used for estimation of several prognostic situations. Methods . Ninety-six clinical and laboratory features from each one of 141 patients who underwent lung resection were retrospectively collected. The variables were used as input data for the software. Cases were divided into a training set (n = 113) and a test set (n = 28). Four NN models were trained using the data from the training set: (1) using all variables; (2) using only the Goldman and Torrington scores; (3) using all variables except for the two scores. A fourth NN was programmed with all variables to estimate the development of major postoperative complications. The trained NN models were tested with the test set data. Results . The NN using all variables with or without the scores were able to correctly classify all 28 test cases against actual outcome. The NN using all variables also estimated major postoperative complications correctly in all 28 test cases. The NN using only two indices (Goldman and Torrington) yielded 6 of 28 errors in classification. Conclusions . These data suggest that NN can integrate results from multiple data predicting the individual outcome for patients, rather than assigning them to less-precise risk group categories.

Little is known about the natural history of resolution of nosocomial pneumonia, and thus it is likely that we are not always using the optimal duration of therapy in all patients. For some patients, with few risk factors for a poor outcome, and infection with easily treated pathogens, we can probably treat with a more abbreviated course of therapy than is commonly used. For other patients with risk factors for a poor outcome, and infection with ;;high risk'' pathogens such as Pseudomonas aeruginosa, we may need longer durations of therapy. We review the clinical and microbiological definitions of resolution, including improvement, delayed resolution, relapse, or recurrent infection. There are also microbiological end points for resoution including eradication, persistence, and superinfection. The clinical parameters that affect resolution are patient related, microbiological, and treatment related, and these factors are summarized here. Currently, the time course of resolution is being defined using clinical end points such as the clinical pulmonary infection score (CPIS) and microbiological end points such as quantitative cultures of respiratory secretions. The hope for the future is to be able to identify whether the clinical response is adequate, at the earliest posible time point. This may allow for interventions to help the nonresponding patient, or shorten the duration of therapy in the responding patient.

The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population–intervention–comparison–outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.

This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs). A systematic search of the biomedical literature (PubMed) was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela) signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%). Gram-negative pathogens, predominantlyAcinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, andEscherichia coli, accounted for>50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

Purpose of review Ventilator-associated pneumonia (VAP) is the most frequent cause of death among the nosocomial infections acquired in the ICU. Routine surveillance endotracheal aspirate (ETA) cultures in patients on mechanical ventilation have been proposed to predict the cause of VAP. Our aim is to review the available experience regarding the role of surveillance ETA cultures in guiding VAP antimicrobial therapy. Recent findings Microorganisms arrive in the lower respiratory tract by aspiration from the oropharynx or gastric reflux, extension from a contiguous infection, air contamination or by hematogenous seeding. Bacterial colonization of the airway leads to the development of VAP and may result from the aspiration of oropharyngeal or gastric secretions. Recent studies have suggested that surveillance cultures could provide a rationale for prescribing appropriate antibiotics, while waiting for culture results, in up to 95% of patients in whom VAP is ultimately diagnosed by bronchoalveolar lavage fluid culture. However, some authors observed that guiding therapy with those routine surveillance cultures leads to unacceptably low coverage of the pathogens producing VAP. Summary This article describes the evidence supporting the use of routine ETA cultures to prescribe appropriate initial empirical therapy compared with the current practice dictated by guidelines.

To assess oxygen desaturation during activities and to evaluate the short-term effects of supplemental O(2) use in patients with severe COPD who do not qualify for long-term O(2) therapy.A double-blind, randomized, placebo-controlled trial.Outpatients from the pulmonary diseases division of a tertiary-care university hospital.Twenty patients with stable COPD with FEV(1)/FVC ratios of50%, FEV(1) levels55% of the predicted normal value, and PaO(2) levels of60 mm Hg when resting.Patients were initially evaluated with pulmonary function tests, blood gas analysis, and Doppler echocardiography, and they underwent the following three 6-min walking tests (WTs) in a random sequence: basal WT (BWT); WT while breathing compressed air (CAWT); and WT while breathing O(2) (O(2)WT).The distance walked was recorded in meters. Dyspnea was measured by Borg scale measurement before and after the tests, and arterial oxygen saturation measured by pulse oximetry (SpO(2)) was continuously monitored. Results were analyzed by grouping patients in the following manner: desaturators (DSs) (ie, patients with a drop in SpO(2) of at least 5% and90% during the WT) vs nondesaturators (NDSs); and O(2) responders (ie, patients with an increase of at least 10% in the distance walked and/or a decrease of at least 3 points in Borg index score) vs nonresponders. During the BWT, 11 of 20 patients (55%) were defined as desaturators. During the O(2)WT, the SpO(2) remained at90% in every patient. The distance walked increased by 22% (p0.02), and dyspnea decreased 36% (p0.01) in DS patients. In NDS patients, O(2) administration reduced dyspnea by 47% (p0.001), but the distance walked did not improve. Responses were markedly different from one patient to another. No significant differences were noticed between the results of the BWT and CAWT in any of the groups. Thirteen O(2) responders did not differ from 7 nonresponders either in basal data or in desaturation measure during the BWT, except that all walking responders (five patients) were above the median of basal left ventricle performance.Most of the studied COPD patients desaturated during the BWT. O(2) administration avoided desaturation and could increase the distance walked and reduce dyspnea, but these effects were not related to walking desaturation in individual cases. Improvements were not a placebo effect. The therapeutic role of O(2) during activities in some patients with severe COPD needs to be individually assessed.

Objective To survey the etiology and epidemiology ofcommunity-acquired pneumonia (CAP) in relation to age, comorbidity, andseverity and to investigate prognostic factors. Design Prospective epidemiologic study, singlecenter. Setting University hospital at Buenos Aires,Argentina. Patients Outpatients and inpatientsfulfilling clinical criteria of CAP. Interventions Systematic laboratory evaluation for determining the etiology, andclinical evaluation stratifying patients into mild, moderate, andsevere CAP (groups 1 to 3), a clinical rule used forhospitalization. Results During a 12-month period,343 patients (mean age, 64.4 years; range, 18 to 102 years) wereevaluated. We found 167 microorganisms in 144 cases (yield, 42%). Streptococcus pneumoniae , the most common pathogen, wasisolated in 35 cases (24%). Mycoplasma pneumoniae ,present in 19 (13%), was second in frequency in group 1; Haemophilus influenzae , present in 17 cases (12%), wassecond in group 2; and Chlamydia pneumoniae , present in12 cases (8%), was second in group 3. Etiology could not be determinedon the basis of clinical presentation; identifying the etiology had noimpact on mortality. Some findings were associated with specificcausative organisms and outcome. A significantly lower number ofnonsurvivors received adequate therapy (50% vs 77%). Conclusions Age, comorbidities, alcohol abuse, and smokingwere related with distinct etiologies. Pao 2 tofraction of inspired oxygen ratio

Purpose. Our objective was to describe the relationship between sepsis syndrome mortality and cognitive and physical disability in elderly persons. Methods. A 1-year consecutive cohort study in clinical beds of a university hospital was performed. Variables were severity of sepsis syndrome, organ failure, functional status, age, sex, and positive cultures. Outcomes were in-hospital and 1-year mortalities. Results. The study included 137 patients (.70 years), both sexes. Data from 116 (84.5%) patients were obtainable at 1-year follow-up. Forty-eight (35%) patients presented with sepsis (11/137, 8%) or severe sepsis (37/137, 27%). Inhospital mortality was 15.3% (0% for sepsis and 21.8% if severe) and increased with organ failure ( p , .0001). One-year mortality was 54.78% (63/116), mostly related to severe sepsis; predictors were severe organ failure ( p , .0001), prior functional status ( p ¼ .0005), and Mini-Mental State Examination ( p ¼ .03). Prior functional status and organ failure were independent predictors. Conclusions. In-hospital and 1-year mortality increased with septic syndrome severity, prior functional status, and organ failure.

To define the impact of BAL data on the selection of antibiotics and the outcomes of patients with ventilator-associated pneumonia (VAP).Prospective observation and bronchoscopy with BAL, performed within 24 h of establishing a clinical diagnosis of a new episode of hospital-acquired VAP or progression of a prior episode of nosocomial pneumonia (NP).A 15-bed medical and surgical ICU.One hundred thirty-two patients hospitalized for more than 72 h, who were mechanically ventilated and had a new or progressive lung infiltrate plus at least two of the following three clinical criteria for VAP: abnormal temperature (38 degrees C or35 degrees C), abnormal leukocyte count (10,000/mm3 or3,000/mm3), purulent bronchial secretions.Bronchoscopy with BAL within 24 h of establishing a clinical diagnosis of VAP or progression of an infiltrate due to prior VAP or NP. All patients received antibiotics, 107 prior to bronchoscopy and 25 immediately after bronchoscopy.Sixty-five of the 132 patients were BAL positive (BAL[+]), satisfying a microbiologic definition of VAP (10(4) cfu/mL), while 67 were BAL negative (BAL[-]). The BAL(+) patients had no differences in mortality, prior antibiotic use, and demographic features when compared with the BAL(-) patients. More of the BAL(+) patients (38/65) satisfied all three clinical criteria of VAP than did BAL(-) patients (24/67) (p0.05). A total of 50 BAL(+) patients received antibiotic therapy prior to bronchoscopy, and when this prior therapy was adequate (n = 16), as defined by the results of BAL, then mortality was 38%, while if prior therapy was inadequate (n = 34), mortality was 91% (p0.001), and if no therapy was given (n = 15), mortality was 60%. When therapy changes were made after bronchoscopy, more patients (n = 42) received adequate therapy, but mortality in this group was comparable to mortality among those who continued to receive inadequate therapy (n = 23). A total of 46 of the 65 BAL(+) patients died, with 23 of these deaths occurring during the 48 h after the bronchoscopy, before BAL results were known. When BAL data became available, 37 of the 42 surviving patients received adequate therapy, but their mortality was comparable to the patients who continued to receive inadequate therapy.Patients with a strong clinical suspicion of VAP have a high mortality rate, regardless of whether BAL cultures confirm the clinical diagnosis of VAP. When adequate antibiotic therapy is initiated very early (ie, before performing bronchoscopy), mortality rate is reduced if this empiric therapy is adequate, compared to when this therapy is inadequate or no therapy is given. If adequate therapy is delayed until bronchoscopy is performed or until BAL results are known, mortality is higher than if it had been given at the time of first establishing a clinical diagnosis of VAP. When patients were changed from inadequate antibiotic therapy to adequate therapy, based on the results of BAL, mortality was comparable to those who continued to receive inadequate therapy. Thus, even if bronchoscopy can accurately define the microbial etiology of VAP, this information becomes available too late to influence survival.

OBJETIVO: Bacteriemia es la forma invasiva más común de neumonía adquirida en la comunidad (NAC) por Streptococcus pneumoniae. Investigamos si la bacteriemia en NAC neumocócica empeora los resultados y si ella guarda relación con la vacunación antineumocócica (VAN). MÉTODOS: Análisis secundario de una cohorte de pacientes con NAC neumocócica confirmada por cultivo de sangre o esputo o antígeno urinario. Se registraron datos demográficos, clínicos, radiográficos y de laboratorio, escores Acute Physiology and Chronic Health Evaluation II (APACHE II) y pneumonia severity index (PSI), comorbilidades y antecedente de VAN. Se compararon pacientes con NAC neumocócica bacteriémica (NNB) vs. no bacteriémica (NNNB). RESULTADOS: Cuarenta y siete pacientes tenían NNB y 71 NNNB (45 por cultivo de esputo y 26 por antígeno urinario); 107 tenían alguna indicación de VAN. Ningún paciente con NNB, pero 9 con NNNB, habían recibido VAN (p = 0,043). Los pacientes con NNB eran mayores (76,4 ± 11,5 vs. 67,5 ± 20,9 años), tenían mayor APACHE II (16,4 ± 4,6 vs. 14,1 ± 6,5) y PSI (129,5 ± 36 vs. 105,2 ± 45), más frecuentemente cardiopatía e insuficiencia renal crónica e internación en UTI (42,5% vs. 22,5%) y menor hematocrito (35,7 ± 5,8 vs. 38,6 ± 6,7%) y sodio plasmático (133,9 ± 6,0 vs. 137,1 ± 5,5 mEq/L). La mortalidad fue similar (29,8% vs. 28,2%). CONCLUSIONES: Los niveles de VAN (8,4%) en esta población con alto riesgo de NAC por S. pneumoniae fueron extremadamente bajos. Los pacientes con NNB estaban más graves, pero la mortalidad fue similar entre los dos grupos. La VAN reduce la incidencia de NNB y es razonable incrementar el nivel de vacunación de la población en riesgo. OBJECTIVE: Bacteremia is the most common presentation of invasive disease in community-acquired pneumonia (CAP) due to Streptococcus pneumoniae. We investigated whether bacteremia in pneumococcal CAP worsens outcomes and whether it is related to pneumococcal vaccination (PV). METHODS: Secondary analysis of a cohort of patients with pneumococcal CAP confirmed by blood culture, sputum culture, or urinary antigen testing. Demographic, clinical, radiographic, and biochemical data were collected, as were Acute Physiology and Chronic Health Evaluation II (APACHE II) and pneumonia severity index (PSI) scores, comorbidities, and PV history. We drew comparisons between patients with bacteremic pneumococcal CAP (BPP) and those with non-bacteremic pneumococcal CAP (NBPP). RESULTS: Forty-seven patients had BPP, and 71 had NBPP (confirmed by sputum culture in 45 and by urinary antigen testing in 26); 107 had some indication for PV. None of the BPP patients had received PV, compared with 9 of the NBPP patients (p = 0.043). Among the BPP patients, the mean age was higher (76.4 ± 11.5 vs. 67.5 ± 20.9 years), as were APACHE II and PSI scores (16.4 ± 4.6 vs. 14.1 ± 6.5 and 129.5 ± 36 vs. 105.2 ± 45, respectively), as well as the rate of ICU admission for cardiopathy or chronic renal failure (42.5% vs. 22.5%), whereas hematocrit and plasma sodium levels were lower (35.7 ± 5.8 vs. 38.6 ± 6.7% and 133.9 ± 6.0 vs. 137.1 ± 5.5 mEq/L, respectively), although mortality was similar (29.8% vs. 28.2%). CONCLUSIONS: In this population at high risk for CAP due to S. pneumoniae, the PV rate was extremely low (8.4%). Although BPP patients were more severely ill, mortality was similar between the two groups. Because PV reduces the incidence of BPP, the vaccination rate in at-risk populations should be increased.

Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality worldwide, and since 1993, guidelines for management have been available. The process, which first began in the United States and Canada, has now been implemented in numerous countries throughout the world, and often each geographic region or country develops locally specific recommendations. It is interesting to realize that guidelines from different regions often interpret the same evidence base differently, and guidelines differ from one country to another, even though the bacteriology of CAP is often more similar than different from one region to another. One of the unique contributions of the 2007 US guidelines is the inclusion of quality and performance measures. In addition, US guidelines emphasize management principles that differ from some of the principles in European guidelines because of unique epidemiological considerations. In addition, certain therapy principles apply in the United States that differ from those in other regions, including the need for all patients to receive routine therapy for atypical pathogens, the emergence of community-acquired methicillin-resistant Staphylococcus aureus in some patients following influenza, and the need for all patients admitted to the intensive care unit to receive at least two antimicrobial agents. In the future, as guidelines evolve, there will be an important place for regional guidelines, particularly if these guidelines can recommend locally specific strategies to implement guidelines, which if successful, can lead to improved patient outcomes.