Collateral damage.
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Anti-Infective Agents↗
Biomedical subjects
Louis B Rice
Publications and source records attributed to Louis B Rice.
Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive?
Mortality related to serious infections in intensive care units (ICUs) is highest if empirical therapy is not active against the organism causing the infection. However, excessive empirical therapy undoubtedly contributes to bacterial resistance to antibiotics, in turn potentially contributing to poor patient outcome. We have reviewed 3 strategies that are increasingly practiced to reduce the hazards of broad empirical therapy, while aiming to ensure that empirical therapy is adequate. The most widely practiced strategy is discontinuation or streamlining of empirical therapy when culture results are available. The second approach is to withdraw certain antibiotic classes (most notably, third-generation cephalosporins) from the ICU antibiotic armamentarium. The third strategy employed is antibiotic cycling. Although this has also appeared to be a successful strategy, currently published studies have used historical controls and thus may be subject to significant bias. Computer-assisted antibiotic prescribing in ICUs may supplement or replace such strategies in the future.
Anti-Bacterial Agents↗
A potential virulence gene, hylEfm, predominates in Enterococcus faecium of clinical origin.
An open reading frame (hyl(Efm)) with homologies to previously described hyaluronidase genes has been identified in nonstool isolates of Enterococcus faecium. E. faecium isolates (n=577) from diverse sources were screened for the presence of hyl(Efm) and esp(Efm), a putative virulence gene associated with epidemic E. faecium strains. The presence of esp(Efm) was roughly twice that of hyl(Efm), but both were found primarily in vancomycin-resistant E. faecium isolates in nonstool cultures obtained from patients hospitalized in the United States. These data suggest that specific E. faecium strains may be enriched in determinants that make them more likely to cause clinical infections. Differences in the prevalence of these strains may help explain variations in the clinical importance of multiresistant E. faecium across different continents.
Anti-Bacterial Agents↗
Do we really need new anti-infective drugs?
Nosocomial infections continue to be important causes of morbidity and mortality in modern hospitals. The large volume and often excessive use of antimicrobial agents, particularly in critical care settings, has led to the emergence of pathogens that are resistant to virtually all available antimicrobial agents. Moreover, patients infected with organisms that are susceptible to one or more agents might not tolerate those agents, leaving physicians with no therapeutic options. Finally, the need to move patients out of the hospital, and thereby avoid nosocomial infections, has created an ever-growing need for antimicrobial agents whose pharmacokinetic profiles favour a single daily dosing that can be administered at home.
Anti-Bacterial Agents↗
Use of denaturing gradient gel electrophoresis for analysis of the stool microbiota of hospitalized patients.
Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified ribosomal RNA gene amplicons was used to study the stool microbiota of hospitalized patients and to examine the effect of antibiotic therapy. For one patient, 16 anaerobic species identified by random cloning and sequencing of PCR-amplified rRNA genes from stool were represented by bands on the DGGE gel. DGGE analysis and similarity index comparisons demonstrated that the anaerobic microbiota of this individual remained stable in the absence of antibiotic therapy, was minimally affected by ciprofloxacin but markedly reduced by clindamycin therapy, and recovery of some organisms was evident within days after discontinuation of clindamycin. DGGE analysis of additional patients demonstrated similar disruptions of the intestinal microbiota associated with antibiotic therapy. The DGGE banding patterns of nine patients showed considerable variability, but several bands were shared among patients. Thus, our findings are consistent with previous studies that utilized culture techniques, and suggest that DGGE is a useful technique for analysis of the stool microbiota of hospitalized patients.
Actinobacteria↗
Recombination proficiency influences frequency and locus of mutational resistance to linezolid in Enterococcus faecalis.
In vitro linezolid resistance was selected at a higher frequency in Enterococcus faecalis JH2-2 than in recombination-deficient E. faecalis UV202. Resistance in JH2-2 was related to accumulated G2576T mutations in 23S rRNA genes, with the least resistance conferred by mutations in two of four copies. UV202 resistance was associated with a G2505A mutation present in a single copy in mutants with different MICs.
Acetamides↗
Extended-spectrum beta-lactamases in Klebsiella pneumoniae bloodstream isolates from seven countries: dominance and widespread prevalence of SHV- and CTX-M-type beta-lactamases.
A huge variety of extended-spectrum beta-lactamases (ESBLs) have been detected during the last 20 years. The majority of these have been of the TEM or SHV lineage. We have assessed ESBLs occurring among a collection of 455 bloodstream isolates of Klebsiella pneumoniae, collected from 12 hospitals in seven countries. Multiple beta-lactamases were produced by isolates with phenotypic evidence of ESBL production (mean of 2.7 beta-lactamases per isolate; range, 1 to 5). SHV-type ESBLs were the most common ESBL, occurring in 67.1% (49 of 73) of isolates with phenotypic evidence of ESBL production. In contrast, TEM-type ESBLs (TEM-10 type, -12 type, -26 type, and -63 type) were found in just 16.4% (12 of 73) of isolates. The finding of TEM-10 type and TEM-12 type represents the first detection of a TEM-type ESBL in South America. PER (for Pseudomonas extended resistance)-type beta-lactamases were detected in five of the nine isolates from Turkey and were found with SHV-2-type and SHV-5-type ESBLs in two of the isolates. CTX-M-type ESBLs (bla(CTX-M-2) type and bla(CTX-M-3) type) were found in 23.3% (17 of 73) of isolates and were found in all study countries except for the United States. We also detected CTX-M-type ESBLs in four countries where they have previously not been described-Australia, Belgium, Turkey, and South Africa. The widespread emergence and proliferation of CTX-M-type ESBLs is particularly noteworthy and may have important implications for clinical microbiology laboratories and for physicians treating patients with serious K. pneumoniae infections.
Bacterial Proteins↗
An interventional program to improve antibiotic use.
BACKGROUND: Large volume and often inappropriate use of specific antimicrobial agents increase selective pressure for emergence of resistant bacteria and place strain on the pharmacy budget. OBJECTIVE: To initiate a multidisciplinary program designed to align intravenous vancomycin and fluoroquinolone prescribing practices with guidelines for appropriate use of these agents. METHODS: A multidisciplinary, prospective interventional program was implemented to encourage early discontinuation of inappropriate vancomycin and fluoroquinolone therapy and decrease inappropriate duplicative gram-negative coverage using fluoroquinolones. A computerized review was performed for patients receiving intravenous vancomycin and fluoroquinolones for 1998 in a Veterans Affairs Medical Center. In June 1999, guidelines were disseminated and an interventional program was initiated, with a monthly conference for medical residents regarding antimicrobial resistance and local hospital practices. Concurrently, a prospective review of new orders was assessed by the clinical pharmacist and interventions performed when inappropriate use occurred. RESULTS: The interventional program was successful in reducing unnecessary duplicative gram-negative coverage with intravenous fluoroquinolones by 26% (p < 0.001) from 1998 to 2001. Overall, a 43% reduction in the number of courses of intravenous fluoroquinolones was seen during these 4 years. Courses lasting >5 days were reduced by 22% (p < 0.001). Vancomycin prescriptions deemed inappropriate that were administered >5 days were reduced by 16% (p < 0.001) during the same time period. The interventions performed by the clinical pharmacist were deemed successful, with a 76% acceptance rate by providers. CONCLUSIONS: Education of physicians through monthly conferences and personal interventions resulted in an increase in appropriate empiric antibiotic use, a decrease in the duration of inappropriate use, and a decrease in duplicate gram-negative coverage.
Anti-Bacterial Agents↗
Controlling antibiotic resistance in the ICU: different bacteria, different strategies.
To reduce antimicrobial resistance in the intensive care unit, hospitals are developing strategies such as improving infection control, adhering to prescribed formularies, requiring prior approval for using certain antibiotics, setting limits on the duration of antimicrobial therapy, and rotating the use of antimicrobial drugs on a regular schedule. Each strategy has theoretical benefits and limitations, but good data on their efficacy in controlling antimicrobial resistance are limited.
Anti-Bacterial Agents↗
Antibiotic-resistant gram-negative organisms in pediatric chronic-care facilities.
This study was designed to define the prevalence of colonization with antibiotic-resistant gram-negative rectal specimens were obtained from subjects residing in 2 pediatric extended-care facilities and were processed to identify gram-negative organisms resistant to ceftazidime, gentamicin, meropenem, and piperacillin-tazobactam. Horizontal transmission was assessed by analyzing all resistant isolates by pulsed-field gel electrophoresis. Forty percent of subjects were colonized with >/=1 resistant bacillus; >60% of organisms were resistant to >/=2 of the antibiotics tested. Colonization was disproportionate among residents with a tracheostomy or other prosthesis. More than 65% of colonized subjects shared 1 organism with another resident, with cross-colonization occurring among both enteric and nonenteric species. Children residing in chronic-care facilities represent a large reservoir for resistant bacilli. Such colonization may be amenable to simple barrier infection-control procedures.
Adolescent↗
A clinical strain of Escherichia coli possessing CMY-2 plasmid-mediated amp C beta-lactamase: an emerging concern in pediatrics?
A 5-year-old child was colonized by an isolate of Escherichia coli that transferred resistance to third-generation cephalosporins and cefoxitin. This resistance phenotype was encoded on a >75-kb plasmid pLRM 22. The transferable plasmid contained both blaCMY-2 and blaTEM-1b. Increasing reports of CMY-2 beta-lactamase in clinical isolates in children raise concerns about the empiric use of third-generation cephalosporins in this patient group.
Bacterial Proteins↗