Viruses are frequently found in the airway of patients with pneumonia requiring ICU admission and may cause severe forms of pneumonia. Patients with viral infection and bacterial infection had comparable mortality rates.

Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter, introduced during the construction of each mutant, followed by hybridization of this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability to identify fitness phenotypes using our pool of mutants, the pool was subjected to selection by intraperitoneal injection into BALB/c mice and subsequent recovery from spleens. Changes in the representation of each mutant were monitored using T7 transcripts hybridized to a novel inexpensive minimal microarray. Among the top 120 statistically significant spleen colonization phenotypes, more than 40 were mutations in genes with no previously known role in this model. Fifteen phenotypes were tested using individual mutants in competitive assays of intraperitoneal infection in mice and eleven were confirmed, including the first two examples of attenuation for sRNA mutants in Salmonella. We refer to the method as Array-based analysis of cistrons under selection (ABACUS).

Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii are characterized by chromosomally encoded AmpC ␤-lactamases and possess the ability to develop resistance upon exposure to broad-spectrum cephalosporins. To determine the incidences of the emergence of resistance during antimicrobial therapy for infections caused by these organisms and the effect of the emergence of resistance on patient outcomes, all patients who were admitted to the Asan Medical Center (Seoul, Republic of Korea) from January 2005 to June 2006 and whose clinical specimens yielded Enterobacter spp., S. marcescens, C. freundii, or M. morganii were monitored prospectively. The main end point was the emergence of resistance during antimicrobial therapy. A total of 732 patients with infections were included for analysis. The overall incidence of the emergence of antimicrobial resistance during antimicrobial therapy was 1.9% (14/732). Resistance to broadspectrum cephalosporins, cefepime, extended-spectrum penicillin, carbapenem, fluoroquinolones, and aminoglycosides emerged during treatment in 5.0% (11/218), 0% (0/20), 2.0% (2/100), 0% (0/226), 0% (0/153), and 1.1% (1/89) of patients, respectively. The emergence of resistance to broad-spectrum cephalosporins occurred more often in Enterobacter spp. (8.3%, 10/121) than in C. freundii (2.6%, 1/39), S. marcescens (0%, 0/37), or M. morganii (0%, 0/21). Biliary tract infection associated with malignant bile duct invasion was significantly associated with the emergence of resistance to broad-spectrum cephalosporins (P ‫؍‬ 0.024 at a significance level of 0.042, by use of the Bonferroni correction). Only 1 of the 14 patients whose isolates developed resistance during antimicrobial therapy died. The emergence of resistance was more frequently associated with broadspectrum cephalosporins than with the other antimicrobial agents tested, especially in Enterobacter spp. However, the emergence of resistance was associated with a low risk of mortality.Enterobacter spp., Serratia marcescens, Citrobacter freundii, and Morganella morganii have emerged as major causes of nosocomial infections caused by gram-negative bacteria. According to recent data from the SENTRY antimicrobial resistance surveillance program, Enterobacter spp., Serratia spp., Citrobacter spp., and M. morganii ranked 4th, 6th, 11th, and 12th, respectively, among the gram-negative organisms that cause bloodstream infections (3). These organisms are characterized by inducible resistance mediated by the chromosomal AmpC ␤-lactamase (12). This type of resistance can emerge rapidly during antimicrobial therapy (2, 9, 10), thus limiting the choice of antimicrobial agents that can be used to treat infections caused by these organisms.A landmark study by Chow et al. showed the emergence of resistance to broad-spectrum cephalosporins in 19% of Enterobacter blood isolates from patients receiving antimicrobial agents of this class (2). Chow et al. suggested that it may be prudent to avoid treatment with broad-spectrum cephal...