Bacteremic Pneumonia Due to Staphylococcus aureus: A Comparison of Disease Caused by Methicillin-Resistant and Methicillin-Susceptible Organisms

Clinical Infectious Diseases, Nov 1999

We performed a prospective study of all patients with bacteremic pneumonia due to Staphylococcus aureus over a period of 6 years during an outbreak of methicillin-resistant S. aureus (MRSA). Patients with bacteremic pneumonia due to MRSA (32 cases) or methicillin-susceptible S. aureus (MSSA; 54 cases) were compared. The patients with MRSA pneumonia were older and were more likely than those with MSSA pneumonia to have predisposing factors for acquisition of the infection. There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA and MSSA pneumonia. Mortality was significantly higher among MSSA-infected patients treated with vancomycin than among those treated with cloxacillin (47% vs. none; P <.01). Multivariate analysis (stepwise logistic regression method) showed a relationship between mortality and the following variables: septic shock (odds ratio [OR], 61), vancomycin treatment (OR, 14), and respiratory distress (OR, 8).

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Bacteremic Pneumonia Due to Staphylococcus aureus: A Comparison of Disease Caused by Methicillin-Resistant and Methicillin-Susceptible Organisms

Carmen Gonza lez 0 2 4 Margarita Rubio 0 2 3 Jose Romero-Vivas 0 2 3 Miguel Gonza lez 0 1 2 Juan J. Picazo 0 2 4 0 Materials and Methods 1 Department of Biostatistics, Universidad de Extremadura , Badajoz , Spain 2 Received 13 January 1999; revised 17 June 1999. Salinero de los Santos , 1 Esc Dcha 37 A, 06011 Badajoz , Spain 3 Department of Medical Specialties, Universidad Europea de Madrid 4 Department of Medical Microbiology, Hospital Universitario San Carlos We performed a prospective study of all patients with bacteremic pneumonia due to Staphylococcus aureus over a period of 6 years during an outbreak of methicillin-resistant S. aureus (MRSA). Patients with bacteremic pneumonia due to MRSA (32 cases) or methicillin-susceptible S. aureus (MSSA; 54 cases) were compared. The patients with MRSA pneumonia were older and were more likely than those with MSSA pneumonia to have predisposing factors for acquisition of the infection. There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA and MSSA pneumonia. Mortality was significantly higher among MSSA-infected patients treated with vancomycin than among those treated with cloxacillin (47% vs. none; P ! .01). Multivariate analysis (stepwise logistic regression method) showed a relationship between mortality and the following variables: septic shock (odds ratio [OR], 61), vancomycin treatment (OR, 14), and respiratory distress (OR, 8). - Pneumonia due to Staphylococcus aureus constitutes 1%10% of cases of community-acquired pneumonia [13] and up to 16% of cases of nosocomial pneumonia [4]. Its clinical manifestations do not appear to differ from those of pneumonias due to other bacterial etiologies [57], and its radiological pattern is heterogeneous [5, 810], in many cases associated with cavitation [5, 8]. The mortality is high [5, 7, 1113]. Numerous epidemic outbreaks of methicillin-resistant S. aureus (MRSA) infection have been reported in hospitals in Europe, the United States, and Australia over the past 3 decades [1422]. In 1990 there began an enormous outbreak of infections due to this microorganism in our hospital, and outbreaks began at the same time in other Spanish hospitals [23]. MRSA pneumonia was the second most frequent infection after surgical wound infection in our center and was a major factor associated with mortality [24]. The high frequency of this infection during MRSA epidemics has also been described in other studies [18, 23]. However, there exist few studies on pneumonia due to this microorganism [12, 25] or comparative analyses indicating the differences between pneumonia due to MRSA and to methicillin-susceptible S. aureus (MSSA) [13, 26]. The difference in virulence of these 2 microorganisms also is not known. We therefore performed a prospective study of Hospital. The Hospital Universitario San Carlos is a tertiary care center with 1479 beds, serving a population of 569,307 inhabitants northwest of the Madrid metropolitan area. During the study period (1 January 1990 to 31 December 1995), 228,177 patients were hospitalized in this center. The hospital has all the medical, surgical, and neonatal specialities, as well as intensive care and postsurgical recovery units. Kidney and bone marrow transplants are performed. There is no burn unit. There is a 16-bed unit for the admission of HIV-infected patients and a day hospital for their outpatient care. Microbiological methods. Samples for microbiological evaluation were taken by bronchial aspiration, bronchoalveolar lavage, and protected specimen brush and for hemoculture. The bronchial aspirates were collected in sterile receptacles. Sample quality was evaluated according to the criteria of Murray and Washington [27], to avoid samples with high levels of oropharyngeal contamination. We consider the finding of S. aureus in pure culture of 2 samples of bronchial aspirate from the same patient on consecutive days to be significant for the diagnosis of pneumonia. Samples were obtained by protected specimen brush according to the technique described by Wimberley [28], and samples were immediately seeded on reaching the laboratory. S. aureus colony counts of >103 cfu/ mL were considered to be significant. Bronchoalveolar lavage was also done by means of bronchoscopy. Quantitative culture was performed on arrival of the samples at the laboratory. S. aureus at >105 cfu/mL was considered significant. Hemocultures were processed by use of the BACTEC-NR 660 system until April 1992 and by use of the BACTEC-NR 860 system after that time (both Becton Dickinson, Sparks, MD). S. aureus was identified by the presence on blood culture of characteristic colonies of gram-positive cocci that were catalaseand coagulase-positive in plasma after 24 h of incubation. Antibiotic sensitivity was determined by the Mueller-Hinton agar diffusion technique, following the recommendations of the National Committee for Clinical Laboratory Standards. Study population. Patients with bacteremic pneumonia due to S. aureus during 1 January 1990 to 31 December 1995 were studied prospectively. The following data were recorded for each patient: age, sex, hospitalization time, length of hospitalization before acquisition of the infection, area of hospitalization, factors predisposing to infection, underlying diseases, and antibiotics used in treating the pneumonia, together with the administration route, dose, and duration of therapy. These patients were followed until their recovery or death. In the case of death, the cause (infection or underlying disease) was recorded. For each of the patients with a blood or respiratory tract sample that yielded S. aureus on culture, all the information available from the microbiology service referring to the isolated microorganism and its antibiotic sensitivity was recorded. Study design. The study included those patients diagnosed as having bacteremic pneumonia due to MRSA or MSSA between 1 January 1990 and 31 December 1995. Epidemiological and clinical characteristics, the clinical evolution, and mortality of the 2 groups were compared. Definition of terms. A diagnosis of pneumonia was made when there existed symptoms of infection of the lower respiratory tract (e.g., cough, purulent expectoration, chest pain) and pulmonary infiltrates on the chest radiograph not attributable to other causes, coinciding with the isolation of S. aureus as the only pathogen in 2 samples of bronchial aspirate taken on consecutive days or in 1 or more of the following samples: protected specimen brush, bronchoalveolar lavage, transthoracic puncture, and/or hemoculture. S. aureus bacteremia was defined as 1 or more hemocultures that were positive for this microorganism. Significant bacteremia was defined as the isolation of S. aureus from at least 1 hemoculture, accompanied by symptoms of clinical sepsis unexplained by other causes. Bacteremic pneumonia was defined as the diagnosis of both pneumonia and significant bacteremia in a patient, by use of the definitions established above. Following the criteria of Finegold [29], aspiration pneumonia was defined as cases in which there was a clear episode of aspiration of particulate matter, foreign body or fluid (normally food), or gastric content in the 72 h prior to the diagnosis of pneumonia. Nosocomial infection was defined as those cases in which the clinical manifestations began 72 h after hospital admission and the sample positive for S. aureus was taken during this period or, alternatively, before this period if the patient had been admitted in the 2 previous weeks. In the cases in which the positive sample (respiratory and/or hemoculture) was obtained before the first 72 h after admission and the patient had not had an admission during the previous 2 weeks, the infection was considered to be community acquired. The presence of neutropenia was defined as a blood polymorphonuclear neutrophil count of <500/mL. There was considered to be prior chemotherapy when there had been oncological chemotherapy in the month preceding the diagnosis of the infection and/or steroid treatment in patients who received a dose of at least 10 mg of prednisone/day (or equivalent) over at least 48 h in the 2 weeks preceding diagnosis of the infection. Underlying diseases were classified according to the criteria of McCabe and Jackson [30] into rapidly fatal, eventually fatal, or nonfatal. Clinical status during the pneumonia episode was classified according to Winston et al. [31] into critical, bad, poor, or stable. An alveolar radiological pattern was defined as the presence of alveolar lesions that appeared as an increase in density of alveoli. This pattern presented with poorly defined and fuzzy margins, tending to coalesce to form a lobar or segmentary distribution or, in the case of massive diffuse affectation, a butterfly wing distribution. An interstitial radiological pattern was defined as the appearance of pulmonary parenchymal lesions in the form of lines, small nodules, or rounded cysts of !1 cm in diameter or a mixture of these. A mixed pattern was defined as the appearance of both alveolar and pulmonary parenchymal lesions. Nodular lung condensations (single or, more frequently, multiple) with sharply defined edges, with or without cavitation, were considered to be septic emboli. Radiologically, lung cavitation was considered to be the presence of a sharp zone of parenchymal loss, delimited by a wall and filled with liquid or air. Pleural effusion was the filling of the pleural cavity with liquid, and empyema was the existence in said cavity of a clearly delimited mass directed toward the lung containing a hydro-aerial level. Shock was defined as a reduction in systolic arterial pressure to !90 mm Hg or in diastolic pressure to !60 mm Hg, accompanied by clinical signs of hypoperfusion, such as oliguria or peripheral vasoconstriction. In patients with previous hypertension, it was defined as a 20% decline in the prior values. Acute renal insufficiency was defined as the sudden appearance of oliguria with an increase in urea and serum creatinine. Respiratory distress was defined as the appearance or aggravation of respiratory insufficiency due to a diffuse disorder of alveolar-capillary permeability, manifested as an increase in pulmonary capillary resistance [32]. Septic hepatopathy was defined as an increase in transaminase and alkaline phosphatase levels above twice the normal values (or above twice the prior value for patients with hepatic disease) after exclusion of other causes of increases in these parameters. The presence of CNS disease was defined as the existence of reduced awareness or the appearance of focal neurological signs. There was considered to be disseminated intravascular coagulation when there was thrombopenia of <80,000 platelets/mL in the presence of fibrin degradation products. Antibiotic treatment. The antibiotic treatment administered and its duration was determined by the clinician. We considered appropriate antibiotic treatment to be the administration of drugs that are active in vitro against the isolated strain of S. aureus, that had recognized clinical efficacy, and that were administered in therapeutic doses. The efficacy of the treatment was considered to be assessable when administration was over a period of at least 48 h, the patient did not die as a consequence of the underlying disease before the completion of the treatment, and the underlying clinical situation allowed the response to the antibiotic treatment to be evaluated. Table 1. Characteristics and underlying diseases of patients with pneumonia due to Staphylococcus aureus. Results NOTE. Data are no. (%) or mean 5 SD. ICU, intensive care unit; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus. a Statistically significant. b Adapted from [30]. Clinical evolution. Clinical evolution was classified as cure when the clinical manifestations disappeared and the cultures became negative and as failure when there was persistence of the clinical manifestations, persistence of positive cultures, or evidence of death directly due to the staphylococcal infection. Death was considered to be due to the staphylococcal infection when at least 1 of the following criteria was satisfied: a culture positive for S. aureus from a sample obtained at the time of death (hemoculture or representative sample from the lower respiratory tract), persistent respiratory symptoms, radiological evidence of the persistence of the pneumonia, or occurrence of death without any explanation within the first 7 days after the diagnosis of staphylococcal pneumonia. Deaths that did not satisfy one of these criteria were considered to be a consequence of the patients underlying disease. Follow-up. The follow-up period was from the diagnosis of pneumonia (by a result positive for S. aureus on culture of a respiratory sample or hemoculture) until cure or death. Statistical analysis. The analysis of variables was done by use of the statistical package BMDP V7.0 (BMDP, West Los Angeles, CA) for UNIX. The Mann-Whitney test was used for the comparison of the quantitative data. Qualitative variables were associated by means of the x2 test and, when the conditions of validity of this test were not fulfilled, by means of Fishers exact test. Statistical significance was considered to be P ! .05. A stepwise logistic regression model was defined, to evaluate the factors associated with mortality due to staphylococcal pneumonia. The magnitude of the effect was measured from the corresponding ORs and from the 95% CIs for the same. General data. During the study period, S. aureus was the cause of 134 cases of bacteremic pneumonia. A total of 36 cases (1 episode/patient) were caused by MRSA (26.9% of the total number of bacteremic pneumonia cases), and 98 cases (73.1%) were due to MSSA. For the comparative analysis between the MRSA and MSSA cases of pneumonia, we excluded those patients who were parenteral drug users (48, 44 with MSSA and 4 with MRSA infections), since nearly all of them had community-acquired MSSA pneumonia with characteristics that were well differentiated from those of the rest of the study population (pulmonary septic emboli from tricuspid endocarditis with unpronounced respiratory symptoms, generally few complications, and a good prognosis). We analyzed 86 patients: 32 (37.2%) with MRSA and 54 (62.8%) with MSSA infections. The epidemic of MRSA infections began in our center at the beginning of 1990, and the percentage of MRSA isolates identified in the microbiology laboratory increased to 56% of the total S. aureus cases in that year. In October 1990, strict control measures were set up, and the frequency of MRSA in the following year varied from 41%54%. A decline in frequency was noticeable by the end of 1992, and at the end of the study period (1995) the percentage of MRSA as a total of S. aureus cases was 20%. Clinical data. Table 1 shows the general characteristics and underlying diseases of the 2 groups of patients. The cases of MRSA pneumonia were most often nosocomial (P ! .01 ), and Table 2. Predisposing factors among patients with pneumonia due to Staphylococcus aureus. Clinical situationb NOTE. Data are no. (%). ICU, intensive care unit; MRSA, methicillinresistant S. aureus; MSSA, methicillin-susceptible S. aureus. a Statistically significant. b Adapted from [31]. Deaths due to infection Deaths in the first 48 h NOTE. Data are no. (%). MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus. the patients with pneumonia due to this microorganism were more elderly than the MSSA-infected patients (P = .01). Also, the mean number of days of hospitalization before acquisition of the pneumonia was significantly greater (P ! .01) for those with MRSA infection. As can be seen in table 1, there were no differences with regard to the areas of hospitalization between the 2 groups of patients. With respect to underlying diseases, it is noteworthy that the mean number of underlying diseases was significantly greater (P = .01) among those with MRSA pneumonia (2.31 5 1.3) than among those with MSSA pneumonia (1.6 5 1.15). The gravity of these underlying diseases was measured according to the criteria of McCabe and Jackson [30]. Of the patients with MRSA pneumonia, 13 (40.6%) were in a rapidly fatal situation, compared with 13 (24.1%) with MSSA pneumonia, but the difference was not significant (P = .1). Lung diseases and vascular diseases were significantly more frequent among the patients with MRSA pneumonia than among those with MSSA pneumonia (34.3% vs. 16.6% [P = .05] and 15.6% vs. 0% [P ! .01], respectively). The factors predisposing to infection are listed in table 2. Of the patients with bacteremic pneumonia due to MRSA, 37.5% had undergone antibiotic treatment before the pneumonia episode, compared with 7.5% of patients with bacteremic pneumonia due to MSSA (P ! .01). The frequencies of previous pneumonia (P = .04), urinary catheters (P ! .01), and central catheters (P ! .01) were significantly higher among patients with MRSA bacteremic pneumonia. The clinical status ratings of the patients, according to the criteria of Winston et al. [31], were very similar in the 2 groups. In the MRSA group, the radiological pattern was alveolar in all patients, as it was in most (47 patients [87%]) of the MSSA group. Also, in this latter group, there were 4 patients (7.4%) with a nodular pattern, 1 (1.9%) with a mixed pattern, and 2 (3.7%) in which the radiological pattern could not be determined. One (3.1%) of the patients with pneumonia due to MRSA developed cavitation, as did 1 (1.9%) of the patients with pneumonia due to MSSA (P = 1). The differences in the percentages of pleural effusion that developed in the 2 groups were also not significant (6.3% MRSA pneumonia vs. 16.7% MSSA pneumonia; P = .19). The involvement was multilobular in 46.9% of the MRSA group and 53.7% of the MSSA group (P = 1.00), and there were no differences between the 2 groups with respect to the presence of diffuse bilateral involvement: 7 patients (21.9%) in the MRSA group and 16 patients (29.6%) in the MSSA group (P = .27). Treatment and evolution. Of the 32 patients with MRSA pneumonia, 22 received appropriate antibiotic treatment, and the evolution of their infection could be evaluated. Of these, 20 were treated with vancomycin (2 of them received some doses of a third-generation cephalosporin during the course of the treatment). Two patients were treated with teicoplanin (associated with co-trimoxazole, and with clindamycin in the other). Of the remaining 10 patients, 8 died within the first 48 h after diagnosis (table 3), 1 died as a consequence of the underlying disease, and 1 had received nonactive antibiotics. Of the total of 54 patients with MSSA pneumonia, 41 received appropriate antibiotic treatment, and the evolution of their infection could be evaluated. Ten patients were treated with cloxacillin, which was associated with aminoglycosides in 3 patients and with third-generation cephalosporins in another 3. Vancomycin was most often used, with 17 patients receiving it (2 received a dose of a third-generation cephalosporin, and another received imipenem during the course of the treatment). Two patients were initially treated with vancomycin and, when the results of the sensitivity of the microorganism were known, had their treatment changed to cloxacillin; in contrast, there were 4 patients whose initial treatment was cloxacillin, which was changed to vancomycin during the course of the infection. Three patients received teicoplanin (associated with a thirdgeneration cephalosporin in 1 patient); other drugs with S. aureus activity (mainly b-lactam antibiotics) were given as treatment to 5 patients: cephalothin plus aminoglycosides, cefotaxime plus erythromycin, and cefotaxime plus clindamycin. Of the remaining 13 patients, 8 died in the first 48 h after diagnosis of the infection (table 3), 4 died as a consequence of the underlying disease, and 1 was moved to another hospital. The mortality associated with the infection was high for both groups of patients. Of the 32 patients with MRSA pneumonia, 18 (56.3%) died as a direct result of the infection, and, of the 54 patients with MSSA pneumonia, 22 (40.7%) died (P = .17; table 3). The percentage of complications that developed was similar for the 2 groups (table 4). Of the 22 patients with MRSA pneumonia who were correctly treated and whose evolution could be evaluated, 11 (50%) died, and of the 41 with MSSA pneumonia, 14 (34%) died (P = .34). The mortality associated with the infection in patients correctly treated with vancomycin was very high in both the MRSA and the MSSA groups (50% vs. 47%; not significant). Table 4. Clinical evolution among patients with pneumonia due to Staphylococcus aureus. NOTE. Data are no. (%). MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus. Table 5. Antibiotic treatment among patients with pneumonia due to Staphylococcus aureus. Group, treatment Cloxacillina No. treated (%) No. who died (%) NOTE. MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus. a P ! .01. The infection-associated mortality among patients with MSSA pneumonia was significantly greater for those treated with vancomycin than for those treated with cloxacillin (47% vs. 0%; P ! .01). These data are given in table 5. Of the total of 63 patients who received appropriate antibiotic treatment and whose clinical evolution could be evaluated, a number of factors were associated with mortality (age, number of underlying diseases, urinary catheter, neurological alterations, septic shock, respiratory distress, acute renal insufficiency, and having undergone treatment with vancomycin). These factors were included in a stepwise logistic regression model, which predicted adequately an average of 85.7% of the observed data. The model showed that vancomycin treatment was independently associated with mortality from the infection and that the risk of death was 14 times greater (OR, 14.5) for vancomycin-treated patients than for those who had received other treatments. Other variables that were found to be independently associated with mortality were septic shock (OR, 61.5) and respiratory distress (OR, 8.3) (table 6). The other variables introduced into the model as potentially important for prognosis (age, number of underlying diseases, neurological alterations, presence of a urinary catheter, and acute renal insufficiency) produced no differences in the ORs of the 3 previously analyzed variables. Considering all the possible interactions among the 3 variablesseptic shock, vancomycin treatment, and respiratory distresswe observed, first, independently of the presence of either of the other 2 variables, that the presence of shock increased the likelihood of death 47-fold (OR, 47.29). Second, in the absence of respiratory distress, vancomycin treatment did not increase mortality. In the presence of distress, however, treatment with vancomycin increased the likelihood of death 38-fold (OR, 38.46) (table 7). Discussion During the last 3 decades, the epidemiology and microbiology of epidemic outbreaks of MRSA infection have been analyzed in a number of studies [1422]. There have been fewer publications, however, describing the characteristics of patients with pneumonia due to MRSA [12, 13, 25, 26]. The epidemic of MRSA infection in our hospital that began in 1990 reached large proportions and is one of the most extensive reported in the literature. This circumstance gave us the opportunity of studying a good number of patients with pneumonia due to MRSA. Of the total cases of bacteremic pneumonia studied, 27% were due to MRSA. The frequency varied from 40% to 50% when those of nosocomial origin were considered, depending on whether the pneumonia was primary or secondary. In general, MRSA pneumonia, as with other infections caused by this organism, is usually of nosocomial origin [7, 12, 33]. There exist no broad studies clarifying its incidence in the community [34]. Some community-acquired cases have been found, however, in series of staphylococcal pneumonia [33] and among cases related to infections in nursing homes [35]. Series of community-acquired MRSA bacteremias have also been described in patients who use drugs parenterally [36, 37]. We had 6 cases of community-acquired pneumonia due to MRSA: 2 elderly patients with aspiration pneumonia and 4 drug-using patients with septic emboli pneumonia. The factors associated with MRSA pneumonia in our patients were advanced age, prolonged hospitalization, gravity of the underlying diseases, especially lung diseases (34.3%), prior antibiotic therapy, and surgery or other invasive maneuvers (vesicular probe, central catheters, and endotracheal intubation). There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA pneumonia, compared with patients with MSSA pneumonia. Our MRSA-infected patients had a high mortality (56.3%). In a study published in 1994, Iwahara et al. [12] analyzed 32 patients with MRSA pneumonia and found these same risk factors for the acquisition of the infection, with the exception of the lung diseases. They did not study MSSA pneumonia. The infection-associated mortality was lower (38%). The greater mortality in our study may be attributed to the high percentage of patients with grave lung disease and to the fact that all the pneumonia cases analyzed were bacteremic. Rello et al. [13], in a comparative study of pneumonia due to MRSA and MSSA in patients in an intensive care unit, found the same epidemiological differences as we did and also described 2 important consequences. First, MRSA pneumonia produced a significantly greater frequency of bacteremia (36.4% vs. 10.5%; RR, 3.4) and septic shock (27.3% vs. 7.9%; RR, 3.4). Second, the infection-associated mortality in their study was greater among the patients with MRSA pneumonia (54.5% vs. 2.6%; RR, 20.7). In the design of our study, all our patients had bacteremic pneumonia, which we then split into MRSA and MSSA bacteremic pneumonia. Therefore, the first conse5.63672.17 1.43145.64 1.4746.08 Table 7. Factors associated with mortality among patients with pneumonia due to Staphylococcus aureus when all possible interactions between shock, vancomycin treatment, and respiratory distress were considered. Septic shock Vancomycin treatment in presence of distress 7.63293.08 3.5422.37 quence of the study of Rello et al. [13] could not be tested, and we think that further studies will have to be done to allow this question to be clarified. Our mortality figures also differed from those of Rello et al. [13]: Although we found a greater mortality among those with pneumonia due to MRSA than among those with pneumonia due to MSSA, the difference was not significant (56.3% vs. 40.7%; P = .17). The high mortality among our patients with MSSA pneumonia was probably influenced by the high proportion of patients who received vancomycin as treatment, a factor that, via the logistic regression model in our design, we found to be directly related to an increase in mortality. The mortality of our MRSA patients who were correctly treated with vancomycin was very high (50%). There are no reports in the literature that allow us to contrast this effect. Recently, Georges et al. [38] demonstrated a low level of vancomycin in the lungs at 24 h after initiation of treatment in 10 patients with MRSA pneumonia. Further studies will be required, however, to confirm the clinical relevance of this finding. In the group of correctly treated patients with MSSA pneumonia, we found that the infection-associated mortality was significantly higher among vancomycin-treated patients (47%) than among those treated with cloxacillin (0%; P ! .01 ). Recent studies [3942] have shown suboptimal results in the treatment of bacteremia and endocarditis with vancomycin; however, this is the first study that shows these suboptimal results in patients with pneumonia due to S. aureus. The reason for these findings has not been clarified. In some in vitro studies, the bactericidal action of vancomycin has been shown to be less and slower than that of cloxacillin [40]. Other authors [42] attribute this poorer effect of vancomycin to its use for treatment of patients with more-grave disease and worse prognosis. In our work, we determined the influence of vancomycin treatment on the mortality among patients with staphylococcal pneumonia. We therefore believe it necessary to carry out future investigations, to perfect the treatment of this infection and to control a series of now known epidemiological factors that may lead to reducing the mortality. 1. Fang GD, Fine M, Orloff J, et al. New emerging etiologies for communityacquired pneumonia with implications for therapy: a prospective multicenter study of 359 cases. Medicine 1990; 69:30716.


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Carmen González, Margarita Rubio, José Romero-Vivas, Miguel González, Juan J. Picazo. Bacteremic Pneumonia Due to Staphylococcus aureus: A Comparison of Disease Caused by Methicillin-Resistant and Methicillin-Susceptible Organisms, Clinical Infectious Diseases, 1999, 1171-1177, DOI: 10.1086/313440