Carlos M. Luna

An International Prospective Study of Pneumococcal Bacteremia: Correlation with In Vitro Resistance, Antibiotics Administered, and Clinical Outcome

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.

Resolution of ventilator-associated pneumonia: prospective evaluation of the clinical pulmonary infection score as an early clinical predictor of outcome.

ObjectivesTo prospectively evaluate the performance of the Clinical Pulmonary Infection Score (CPIS) and its components to identify early in the hospital course of ventilator-associated pneumonia (VAP) which patients are responding to therapy. DesignProspective, multicenter, in a cohort of mechanically ventilated patients. SettingThe intensive care unit of six hospitals located in the metropolitan area of Buenos Aires, Argentina. PatientsSixty-three patients, from a cohort of 472 mechanically ventilated patients hospitalized for >72 hrs, had clinical evidence of VAP and bacteriologic confirmation by bronchoalveolar lavage (BAL) or blood cultures. InterventionsBronchoscopy with BAL fluid culture and blood cultures after establishing a clinical diagnosis of VAP. All patients received antibiotics, 46 before bronchoscopy and 17 immediately after bronchoscopy. Measurements and ResultsCPIS was measured at 3 days before VAP (VAP-3); at the onset of VAP (VAP); and at 3 (VAP+3), 5 (VAP+5), and 7 (VAP+7) days after onset. CPIS rose from VAP-3 to VAP and then fell progressively in the population as a whole (p < .001), and the fall in CPIS was significant in 31 survivors, but not in 32 nonsurvivors. From the individual components of the CPIS, only the Pao2/Fio2 ratio distinguished survivors from nonsurvivors, beginning at VAP+3. When CPIS was <6 at 3 or 5 days after VAP onset, mortality was lower than in the remaining patients (p = .018). These differences also related to the finding that those receiving adequate therapy had a slight fall in CPIS and a significant increase of Pao2/Fio2 at VAP+3, whereas those getting inadequate therapy did not. ConclusionsSerial measurements of CPIS can define the clinical course of VAP resolution, identifying those with good outcome as early as day 3, and could possibly be of help to define strategies to shorten the duration of therapy.

Telavancin versus Vancomycin for Hospital-Acquired Pneumonia due to Gram-positive Pathogens

The results from two methodologically identical double-blind studies indicate that telavancin is noninferior to vancomycin based on clinical response in the treatment of hospital-acquired pneumonia due to Gram-positive pathogens.

Appropriateness and delay to initiate therapy in ventilator-associated pneumonia.

Inappropriate therapy (IT) and delayed initiation of appropriate therapy (DIAT) result in inadequate therapy in patients with ventilator-associated pneumonia (VAP). The aim of the current study was to assess the impact of DIAT in VAP. A total of 76 mechanically ventilated patients with bacteriologically confirmed VAP were prospectively evaluated in the intensive care unit of six hospitals in Buenos Aires, Argentina. Appropriate therapy was defined as coverage of all the identified pathogens by the antimicrobial therapy administered at the time of VAP clinical diagnosis. The clinical pulmonary infection score was measured during the 3 days before, at the onset and during the days which followed the onset of VAP. A total of 24 patients received adequate therapy; mortality was 29.2%. The remaining 52 patients received either IT (n = 16) or DIAT (n = 36); the mortality was 63.5% combined, and 75.0 and 58.3% for IT and DIAT, respectively (statistically significant compared with adequate therapy). Inappropriate therapy and delayed initiation of appropriate therapy increased the mortality of ventilator-associated pneumonia. Patients with inappropriate therapy and/or delayed initiation of appropriate therapy had a more gradual increase in clinical pulmonary infection score than those receiving adequate therapy, and this increase was found to occur prior to the time of the clinical diagnosis. In conclusion, these findings might provide the rationale for a trial of earlier initiation of therapy, based on clinical grounds in an effort to improve the outcome of patients with ventilator-associated pneumonia.

Association of Serotypes of Streptococcus pneumoniae with Disease Severity and Outcome in Adults: An International Study

BACKGROUND The introduction of conjugate pneumococcal vaccination for children has reduced the burden of invasive disease due to pneumococcal conjugate vaccine (PCV) types (i.e., serotypes 9V, 14, 6B, 18C, 23F, 19F, and 4) in adults. As nonvaccine serotypes become predominant causes of invasive disease among adults, it is necessary to evaluate the disease severity and mortality associated with infection due to nonvaccine serotypes, compared with PCV serotypes, in adults. METHODS The association of pneumococcal serotype and host-related variables with disease severity and mortality was statistically examined (with multivariable analysis) in 796 prospectively enrolled, hospitalized adult patients with bacteremia due to Streptococcus pneumoniae. RESULTS In multivariate analyses of risk in patients with invasive pneumococcal disease, older age (age, > or = 65 years; P = .004), underlying chronic disease (P = .025), immunosuppression (P = .035), and severity of disease (P < .001) were significantly associated with mortality; no association was found between nosocomial infection with invasive serotypes 1, 5, and 7 and mortality. The risk factors meningitis (P = .001), suppurative lung complications (P < or = .001), and preexisting lung disease (P = .051) were significantly associated with disease severity, independent of infecting serotype. No differences were seen in disease severity or associated mortality among patients infected with PCV serotypes, compared with patients infected with nonvaccine serotypes. CONCLUSIONS Our data support the notion that host factors are more important than isolate serotype in determining the severity and outcome of invasive pneumococcal disease and that these outcomes are unlikely to change in association with nonvaccine serotype infection in the post-conjugate vaccine era.

Evolution of methicillin-resistant Staphylococcus aureus clones in Latin America

OBJECTIVES Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent nosocomial bacterial pathogen, associated with significant morbidity and mortality. The global incidence is increasing, and Latin America is no exception. This article reviews MRSA clonal distribution in Latin America and implications for clinical practice. DESIGN A PubMed literature search (1966-2008) identified 32 articles that characterized MRSA clones in Latin America. RESULTS Data from these articles show that since 1990, several epidemic MRSA clones have spread in Latin America. The multidrug-resistant Brazilian clone is widespread, especially in Brazil and Argentina, but more recently clones with susceptibility to a range of antibiotics have been detected in Brazil, whereas in Argentina, as in Chile, Colombia and Paraguay, the multidrug-resistant Cordobes/Chilean clone prevails. In Mexico, the New York/Japan clone is most frequent. Data were not available from every country and, despite the increasing prevalence of community MRSA infections, most were collected from tertiary care centers. CONCLUSIONS A variety of epidemic MRSA clones are circulating in Latin America, some of which harbor genes that encode multidrug resistance or enhanced pathogenicity. Continued collection and reporting of epidemiological data is crucial for effective prevention and treatment.

Epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) in Latin America

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.

Effects of glucocorticoids in ventilated piglets with severe pneumonia

There is clinical evidence suggesting that glucocorticoids may be useful in severe pneumonia, but the pathogenic mechanisms explaining these beneficial effects are unknown. The aim of the present study was to determine the effects of adding glucocorticoids to antibiotic treatment in an experimental model of severe pneumonia. In total, 15 Lagerwhite-Landrace piglets were ventilated for 96 h. After intubation, a 75 mL solution containing Pseudomonas aeruginosa (106 cfu·mL−1) was bronchoscopically inoculated. The animals were randomised into three groups 12 h after inoculation: 1) untreated; 2) treated with ciprofloxacin; and 3) treated with ciprofloxacin plus methylprednisolone. Physiological and laboratory parameters were monitored throughout the study. Pro-inflammatory cytokines were measured in serum and bronchoalveolar lavage (BAL). Histopathology of the lungs and cultures from blood, BAL and lungs were performed. At the end of the study, piglets receiving the antibiotic plus glucocorticoids showed: 1) a decrease in the concentration of interleukin-6 in BAL; and 2) a decrease in the global bacterial burden both in BAL and lung tissue. In conclusion, in this experimental model of pneumonia, the association of glucocorticoids with antibiotics attenuates local inflammatory response and decreases bacterial burden in the lung.

Nosocomial Acinetobacter pneumonia

Abstract:  Acinetobacter spp. (A. baumannii is the prevalent genomic species, but others may cause infection) has become an increasingly important cause of nosocomial pneumonia, particularly in mechanically ventilated patients (VAP). This organism has intrinsic resistance to some antimicrobials but easily acquires resistance to many others; Acinetobacter spp. can survive for long periods of time in the environment. All of these characteristics have contributed to protracted outbreaks associated with significant morbidity and mortality. High rates of colonization are found in debilitated hospitalized patients. Infecting or colonizing organisms in nosocomial infections are more likely to be from cross‐transmission or from the hospital environment than from endogenous sources. VAP caused by Acinetobacter spp. is emerging as a prominent hospital complication. The incidence of this microorganism varies from site to site, but it is the second commonest aetiological agent among the gram‐negative bacteria. Longer periods of hospitalization, longer time on mechanical ventilation and prior use of antibiotics are the recognized factors increasing the risk of VAP due to Acinetobacter spp. Treatment needs to clearly differentiate infection from colonization, and the agents with the most antimicrobial activity are imipenem/cilastatin, amikacin, colistin, ampicillin/sulbactam and tigecycline. Monotherapy can be adequate if the patient does not have significant comorbidities. Infection control procedures have a major role to play in preventing transmission of this microorganism. Emphasis on initial control measures should, however, be on strict isolation of infected or colonized patients to limit dissemination of outbreak strains in the environment. The variety of potential sources of contamination with Acinetobacter spp. in the hospital environment makes control of these outbreaks one of the more difficult challenges. Persistence of Acinetobacter spp. in the environment provides ample opportunities for contamination of patients and staff and may explain continuing long‐term outbreaks.

Clinical and economic burden of pneumonia among adults in Latin America

The 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.