Fluoride is widely used as an anticaries agent in drinking water and a variety of other vehicles. This use has resulted in major health benefits. However, there are still open questions regarding the mechanisms of anticaries action and the importance of antimicrobial effects in caries reduction. Fluoride acts in multiple ways to affect the metabolism of cariogenic and other bacteria in the mouth. F(-)/HF can bind directly to many enzymes, for example, heme-containing enzymes or other metalloenzymes, to modulate metabolism. Fluoride is able also to form complexes with metals such as aluminum or beryllium, and the complexes, notably AlF(4)(-) and BeF(3)(-).H(2)O, can mimic phosphate with either positive or negative effects on a variety of enzymes and regulatory phosphatases. The fluoride action that appears to be most important for glycolytic inhibition at low pH in dental plaque bacteria derives from its weak-acid properties (pK(a)=3.15) and the capacity of HF to act as a transmembrane proton conductor. Since many of the actions of fluoride are related to its weak-acid character, it is reasonable to compare fluoride action to those of organic weak acids, including metabolic acids, food preservatives, non-steroidal anti-inflammatory agents and fatty acids, all of which act to de-energize the cell membrane by discharging DeltapH. Moreover, with the realization that the biofilm state is the common lifestyle for most microorganisms in nature, there is need to consider interactions of fluoride and organic weak acids with biofilm communities. Hopefully, this review will stimulate interest in the antimicrobial effects of fluoride or other weak acids and lead to more effective use of the agents for disease control and other applications.

Background-Contact precautions are recommended for interactions with patients colonized/ infected with multidrug-resistant organisms; however, rates of contact precautions practice are unknown.

Prokaryotic secretion relies on proteins that are widely conserved, including NTPases and secretins, and on proteins that are system specific. The Tad secretion system in Aggregatibacter actinomycetemcomitans is dedicated to the assembly and export of Flp pili, which are needed for tight adherence. Consistent with predictions that RcpA forms the multimeric outer membrane secretion channel (secretin) of the Flp pilus biogenesis apparatus, we observed the RcpA protein in multimers that were stable in the presence of detergent and found that rcpA and its closely related homologs form a novel and distinct subfamily within a well-supported gene phylogeny of the entire secretin gene superfamily. We also found that rcpA-like genes were always linked to Aggregatibacter rcpB-or Caulobacter cpaD-like genes. Using antisera, we determined the localization and gross abundances of conserved (RcpA and TadC) and unique (RcpB, RcpC, and TadD) Tad proteins. The three Rcp proteins (RcpA, RcpB, and RcpC) and TadD, a putative lipoprotein, localized to the bacterial outer membrane. RcpA, RcpC, and TadD were also found in the inner membrane, while TadC localized exclusively to the inner membrane. The RcpA secretin was necessary for wild-type abundances of RcpB and RcpC, and TadC was required for normal levels of all three Rcp proteins. TadC abundance defects were observed in rcpA and rcpC mutants. TadD production was essential for wild-type RcpA and RcpB abundances, and RcpA did not multimerize or localize to the outer membrane without the expression of TadD. These data indicate that membrane proteins TadC and TadD may influence the assembly, transport, and/or function of individual outer membrane Rcp proteins.Aggregatibacter (formerly Actinobacillus) actinomycetemcomitans is a gram-negative, capnophilic coccobacillus, principally known as the etiologic agent of localized aggressive periodontitis (16,25,39). A. actinomycetemcomitans is occasionally able to colonize sites outside of the oral cavity to produce other infections, and it is one of the so-called HACEK organisms, gram-negative bacteria that cause approximately 3% of infective endocarditis cases (20). Clinical isolates of A. actinomycetemcomitans adhere to surfaces nonspecifically and form remarkably strong biofilms (14,15,29). Insertional mutagenesis studies have shown that genes of the tad (tight adherence) locus are necessary for the nonspecific adherence of the bacterium to surfaces, as well as for the phenotypes of rough colony morphology, autoaggregation, and production of type IVb Flp pili (29,31,42,45). Genetic and biochemical analyses have indicated that 13 tad gene products are involved (3,29,31,42,45,66); only the flp-2 product is not (42).tad loci have been identified in over half of the sequenced bacteria and in all of the archaeal genomes that have been completed (45,52). Phylogenetic evidence strongly indicates that many bacterial species have acquired the tad genes from foreign sources, and because of its apparent propensity for horizontal transfer, the tad lo...

Compared with agar dilution, other susceptibility testing methods give high rates of apparent false polymyxin susceptibility for cystic fibrosis isolates of P. aeruginosa and S. maltophilia. Prospective study of the correlation between in vitro susceptibility and clinical response is needed to clarify whether these discrepancies reflect oversensitivity of the agar dilution method or insensitivity of the other methods.

We report MIC agreement and error rates between broth microdilution (BMD), Vitek 2, and Etest against 48 clinical KPC-producing Klebsiella pneumoniae isolates for polymyxin B, tigecycline, cefepime, and meropenem. Both commercial testing methods were useful for tigecycline testing; Etest provided a conservative estimate of polymyxin B susceptibility. We suggest that laboratories consider the supplemental use of reference BMD or Etest for cefepime and meropenem for susceptibility testing of KPC-producing K. pneumoniae, as Vitek 2 did not provide reliable results.Carbapenems are considered the broadest-spectrum ␤-lactam agents and are often required for treatment of severe hospital-acquired infections caused by multidrug-resistant Gram-negative organisms. In recent years, plasmid-mediated serine-based ␤-lactamases capable of hydrolyzing carbapenems, as well as other ␤-lactams, have become increasingly prevalent worldwide and are now endemic in geographically diverse areas, including New York City (2, 9, 15). These enzymes, described as Klebsiella pneumoniae carbapenemases (KPCs), are most commonly harbored by K. pneumoniae, and the plasmids that encode KPCs frequently carry resistance genes for other antimicrobial classes, including fluoroquinolones and aminoglycosides (1,12,15).Due to a lack of active antimicrobial agents, therapeutic options are limited for K. pneumoniae isolates expressing KPCs, and optimal treatment is currently unknown. Treatment regimens often consist of various combinations of antibiotics that demonstrate in vitro activity, which might include polymyxin B, tigecycline, and/or a broad-spectrum ␤-lactam at pharmacodynamically optimized doses (12,14). Selection of combination regimens may be guided by the results of antimicrobial susceptibility and/or synergy testing, but there is increasing concern that the results of commercially available susceptibility testing assays for KPC-producing K. pneumoniae may indicate false susceptibility for some agents, although the frequency of this is unknown (1,3,19). In this study, we compared three susceptibility testing methods (broth microdilution [BMD], Vitek 2, and Etest) to determine the rates of MIC agreement for polymyxin B, tigecycline, cefepime, and meropenem among KPC-producing K. pneumoniae clinical isolates. MATERIALS AND METHODSBacterial isolates. This substudy was part of a larger multicenter study of hospital-acquired infections caused by extremely drug-resistant Gram-negative bacilli (XDR-GNB), defined as strains resistant to all but one first-line agent (8). From January 2008 to March 2010, case subjects with bacteremia, pneumonia, or urinary tract infections caused by XDR-GNB were enrolled. Infections were validated using National Healthcare Safety Network definitions (13). K. pneumoniae isolates associated with these infections were tested for bla KPC by PCR as previously described (9). MIC testing. MIC testing was performed using BMD (Trek Diagnostics Systems, Inc., Cleveland, OH), Vitek 2 (bioMérieux Inc., Durham, NC), and Etest (bioMé...