Since carbapenemase-producing Klebsiella pneumoniae strains were first reported in North Carolina, these highly resistant organisms have been isolated with increasing frequency, especially in the New York City area. Polymyxin B is one of the few antimicrobials that retain reliable activity against these organisms. However, polymyxin B MICs are elevated against K. pneumoniae isolates with increasing frequency, leaving clinicians with few therapeutic options. We investigated several antimicrobial agents for potential synergy with polymyxin B against 12 clinical strains of carbapenemase-producing K. pneumoniae. A broth microdilution assay using a 96-well plate was developed in which graded dilutions of polymyxin B and the study drug were incubated with resistant isolates in a checkerboard pattern. Polymyxin B was studied in combination with cefazolin, ceftriaxone, cefepime, imipenem, gentamicin, tigecycline, doxycycline, and rifampin. All K. pneumoniae strains tested positive for K. pneumoniae carbapenemase (KPC) genes by real-time PCR and had elevated polymyxin B MIC values ranging from 16 to 128 g/ml. Synergy was observed with the combination of polymyxin B and rifampin as well as with polymyxin B and doxycycline, resulting in at least a 4-fold decrease in the polymyxin B MIC. For both combinations, this effect occurred at physiologically achievable concentrations. Less pronounced synergy was noted with tigecycline and polymyxin B. No synergy was observed at physiologic concentrations with the other antimicrobials studied. These results suggest that rifampin, doxycycline, and tigecycline may be useful additions to polymyxin B in the treatment of infections caused by highly resistant carbapenemaseproducing K. pneumoniae. Further studies are warranted to determine if these in vitro findings translate into clinical efficacy.

Multilocus DNA sequencing has identified a nonarchetypal strain of Toxoplasma gondii as the causal agent of a waterborne outbreak in Brazil in 2001. The strain, isolated from a water supply epidemiologically linked to the outbreak, was virulent to mice, and it has previously been identified as BrI. Using a serologic assay that detects strain-specific antibodies, we found that 13 (65%) of 20 individuals who were immunoglobulin (Ig) M positive during the outbreak possessed the same serotype as mice infected with the purported epidemic strain. The remaining 7 individuals, plus additional IgM-negative, IgG-positive individuals, possessed 1 of 4 novel serotypes, the most common of which matched the serotype of mice infected with strains isolated from chickens foraging near the outbreak site. The latter strains likely reflect the genetic diversity of T. gondii circulating in highly endemic regions of Brazil. The serotyping assay proved a useful tool for identification of specific individuals infected with the outbreak agent.

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Objectives: To document resistance patterns of three important nosocomial pathogens, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, present in hospitals in Brooklyn, NY.Methods: Susceptibility profiles of pathogens gathered during a surveillance study in 2006 were analysed and compared with similar surveys performed in 1999 and 2001. MICs were determined according to CLSI standards, and selected isolates were screened by PCR for the presence of VIM, IMP and KPC b-lactamases.Results: For P. aeruginosa, susceptibility to most antimicrobials fell in 2001 and then reached a plateau. However, there was a progressive decrease in the number of patients with P. aeruginosa during the three surveys. While the total number of isolates of A. baumannii remained steady, there was a progressive decrease in susceptibility to most classes of antimicrobial agents, and approximately one-third had combined resistance to carbapenems, fluoroquinolones and aminoglycosides. There was a noticeable rise in the number of isolates of K. pneumoniae over the surveillance periods, suggesting that this has become the predominant pathogen in many medical centres. Over one-third of K. pneumoniae collected in 2006 carried the carbapenemase KPC, and 22% were resistant to all three classes of antimicrobial agents.Conclusions: Hospitals in our region have been beset with antimicrobial-resistant Gram-negative bacteria. K. pneumoniae has rapidly emerged as the most common multidrug-resistant pathogen. Improved therapeutic agents and methods of detection are needed to reduce transmission of these bacteria.

In this study, the possible toxic effects of Alternariol Methyl Ether (AME) and Tenuazonic Acid (TeA) produced by Alternaria species on esophagu s of mice were investigated by using light and electron microscopy techniques. Mice were orally fed daily with AME or TeA for 10 months and at the end of this period, the effects of these chemicals on the esophagea l mucosa were determined. By light microscopi c examination, moderate and severe dysplasia characterized by loss of polarity, nuclear pleomorphism , and hyperchromasi a were observed in TeA-treated animals. Electron-microscopi c examination of TeA-treated mucosal epithelial cells revealed pyknosis in some nuclei, granulation and increase in chromatin mass, irregularities in the nuclear contours, vacuolization in nucleoplasms , and marked pleomorphism in the nuclei. In conclusion, our results suggested that TeA has higher toxicity as evidenced by dysplastic transformation.