RESUMEN
BACKGROUND: Primary health care-associated bloodstream infections (PHA-BSIs) affect as many as 350 000 patients in the United States annually. Whereas gram-negative organisms were the leading cause before the 1970s, gram-positive organisms have been the predominant microbial isolates since then. METHODS: We identified all PHA-BSIs among adult inpatients in a 625-bed quaternary care hospital from January 1, 1996, through December 31, 2003, and evaluated trends in the microbial etiology, geographic distribution within the institution, and antimicrobial susceptibilities. RESULTS: A total of 3662 PHA-BSIs caused by 4349 bacterial and fungal isolates were identified. From 1999 to 2003, the proportion of PHA-BSIs due to gram-negative organisms increased from 15.9% to 24.1% (P<.001 for trend). This trend was not significantly different across various units of the hospital, and no specific gram-negative species contributed disproportionately to the increase. With few exceptions, there were no significant increases in antimicrobial resistance. The increase in gram-negative organisms was accompanied by a decline in the proportion of PHA-BSIs from coagulase-negative staphylococci (from 33.5% in 1999 to 29.9% in 2003, P = .007) and from Staphylococcus aureus (from 18.8% in 1999 to 11.8% in 2003, P = .004). The proportion of PHA-BSIs from Candida species almost doubled from 5.8% in 1999 to 11.3% in 2003 (P = .002). CONCLUSIONS: To our knowledge, this is the first US study to report a reemergence of gram-negative organisms as a cause of PHA-BSIs. This finding does not seem to be related to changes in specific gram-negative organisms or to antimicrobial resistance. If this trend continues, it will have important implications for the management of bloodstream infections.
Asunto(s)
Bacteriemia/epidemiología , Infección Hospitalaria/epidemiología , Infecciones por Bacterias Gramnegativas/epidemiología , Hospitales Universitarios/estadística & datos numéricos , Atención Primaria de Salud , Adulto , Bacteriemia/microbiología , Infección Hospitalaria/microbiología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Incidencia , Pennsylvania/epidemiología , Estudios RetrospectivosRESUMEN
In the absence of adequate levels of cellular acidic phospholipids, Escherichia coli remain viable but are arrested for growth. Expression of a DnaA protein that contains a single amino acid substitution in the membrane-binding domain, DnaA(L366K), in concert with expression of wild-type DnaA protein, restores growth. DnaA protein has high affinity for ATP and ADP, and in vitro lipid bilayers that are fluid and contain acidic phospholipids reactivate inert ADP-DnaA by promoting an exchange of ATP for ADP. Here, nucleotide and lipid interactions and replication activity of purified DnaA(L366K) were examined to gain insight into the mechanism of how it restores growth to cells lacking acidic phospholipids. DnaA(L366K) behaved like wild-type DnaA with respect to nucleotide binding affinities and hydrolysis properties, specificity of acidic phospholipids for nucleotide release, and origin binding. Yet, DnaA(L366K) was feeble at initiating replication from oriC unless augmented with a limiting quantity of wild-type DnaA, reflecting the in vivo requirement that both wild-type and a mutant form of DnaA must be expressed and act together to restore growth to acidic phospholipid deficient cells.