Biomedical subjects

Curtis J Donskey

Publications and source records attributed to Curtis J Donskey.

At least 37 records · Page 2Linked to original sources

PubMed2004

The role of the intestinal tract as a reservoir and source for transmission of nosocomial pathogens.

The intestinal tract provides an important reservoir for many nosocomial pathogens, including Enterococcus species, Enterobacteriaciae, Clostridium difficile, and Candida species. These organisms share several common risk factors and often coexist in the intestinal tract. Disruption of normal barriers, such as gastric acidity and the indigenous microflora of the colon, facilitates overgrowth of pathogens. Factors such as fecal incontinence and diarrhea contribute to the subsequent dissemination of pathogens into the health care environment. Selective pressure exerted by antibiotics plays a particularly important role in pathogen colonization, and adverse effects associated with these agents often persist beyond the period of treatment. Infection-control measures that are implemented to control individual pathogens may have a positive or negative impact on efforts to control other pathogens that colonize the intestinal tract.

Animals↗

PubMed2004

Beta-lactam antibiotics and gastrointestinal colonization with vancomycin-resistant enterococci.

We studied the effect of different subcutaneously administered beta-lactam antibiotics on the establishment of gastrointestinal colonization by vancomycin-resistant Enterococcus faecium C68 in a mouse model. Aztreonam, cefazolin, cefepime, and, to a lesser extent, ceftazidime, which neither have significant antienterococcal activity nor are secreted into human bile at high concentrations, did not promote significant vancomycin-resistant enterococci (VRE) colonization. Piperacillin-tazobactam, which has antienterococcal activity and is secreted in human bile at high concentrations, inhibited colonization after limited exposure to the inoculum but was associated with progressively increased VRE colony counts in stool samples after repeated exposure to the VRE inoculum. Ceftriaxone and cefotetan, which lack antienterococcal activity but are secreted into human bile at high concentrations, were associated with rapid and high-level colonization. These data suggest that the risk of VRE colonization varies during exposure to different beta-lactam antimicrobial agents and that the risk is related to biliary concentration and antienterococcal activity of the specific beta-lactam.

Animals↗

PubMed2004

Inhibition of vancomycin-resistant enterococcus by continuous-flow cultures of human stool microflora with and without anaerobic gas supplementation.

A continuous-flow competitive exclusion (CFCE) culture model of human stool microflora was used to examine whether supplemental anaerobic gas is necessary for maintenance of anaerobes and inhibition of vancomycin-resistant Enterococcus (VRE). CFCE cultures of human stool microflora were maintained with supplemental nitrogen, without supplemental nitrogen, or with percolated room air. Cultures with or without supplemental nitrogen maintained >9 log(10) CFU mL(-1) of obligate anaerobes and eliminated 10(6) CFU mL(-1) of VRE. When room air was percolated into the culture, anaerobes were detected at < or =2 log(10) CFU mL(-1), and the same VRE inoculum was not eliminated ( P < 0.001). These data demonstrate that human stool CFCE cultures maintain high levels of obligate anaerobes and inhibit VRE without the addition of supplemental anaerobic gas.

Aerobiosis↗

PubMed2004

The Role of the Intestinal Tract As a Source for Transmission of Nosocomial Pathogens.

The intestinal tract provides an important source for transmission of many nosocomial pathogens, including Enterococcus species, Clostridium difficile, Candida species, Enterobacteriaceae, and other gram-negative bacilli. Recent data suggest that the intestinal tracts of hospitalized patients may also be an important reservoir of Staphylococcus aureus. Although the clinical manifestations of these pathogens are diverse, a common pathogenesis is involved in their colonization of and dissemination from the intestinal tract. Of particular importance is the role that antibiotic selective pressure plays in promotion of colonization by antibiotic-resistant pathogens. Strategies to limit the spread of these pathogens must include efforts to improve adherence to standard infection control practices and promotion of good antimicrobial stewardship. New strategies that include application of novel technologies to the problem of pathogen transmission are needed, and additional research is needed to clarify the potential utility of selective decontamination of the digestive tract.

Journal Article↗

PubMed2004

Acquisition of nosocomial pathogens on hands after contact with environmental surfaces near hospitalized patients.

We examined the frequency of acquisition of bacterial pathogens on investigators' hands after contacting environmental surfaces near hospitalized patients. Hand imprint cultures were positive for one or more pathogens after contacting surfaces near 34 (53%) of 64 study patients, with Staphylococcus aureus and vancomycin-resistant Enterococcus being the most common isolates.

Bacteria↗

PubMed2004

Increased susceptibility to vancomycin-resistant Enterococcus intestinal colonization persists after completion of anti-anaerobic antibiotic treatment in mice.

BACKGROUND: Antibiotic-associated disruption of the indigenous intestinal microflora may persist beyond the treatment period. Although piperacillin/tazobactam inhibits the establishment of vancomycin-resistant Enterococcus (VRE) stool colonization in mice during treatment, we hypothesized that this agent and other anti-anaerobic antibiotics would increase susceptibility to colonization during the period of recovery of the intestinal microflora. DESIGN: Mice received 10(4) colony-forming units of vancomycin-resistant E. faecium by orogastric inoculation 2, 5, or 10 days after completing 5 days of subcutaneous antibiotic treatment, or both during and 2 days after the completion of treatment. Denaturing gradient gel electrophoresis (DGGE) was performed to assess changes in the intestinal microflora. RESULTS: Anti-anaerobic antibiotics (ie, piperacillin/ tazobactam, cefoxitin, and clindamycin) caused significant disruption of the indigenous microflora (mean DGGE similarity indices < or = 27% in comparison with saline controls) and promoted the establishment of high-density colonization when VRE was inoculated 2 or 5, but not 10, days following treatment (P < .001). Piperacillin/tazobactam exhibited a biphasic effect on the establishment of colonization (ie, inhibition when exposed to VRE during treatment and promotion when exposed to VRE after discontinuation of treatment), resulting in greater overall promotion of colonization than did agents with minimal anti-anaerobic activity (ie, levofloxacin, cefepime, and aztreonam) when VRE was inoculated both during and 2 days after treatment (P < .001). CONCLUSION: Patients receiving anti-anaerobic antibiotics, including piperacillin/tazobactam, may be susceptible to the establishment of high-density VRE colonization during the period of recovery of the anaerobic microflora.

Animals↗

PubMed2004

Effect of the increasing use of piperacillin/tazobactam on the incidence of vancomycin-resistant enterococci in four academic medical centers.

BACKGROUND: The substitution of piperacillin/tazobactam, ampicillin/sulbactam, or both for third-generation cephalosporins has been associated with reduced vancomycin-resistant enterococci (VRE). However, piperacillin/tazobactam came into widespread use during a period in which the prevalence of VRE increased. We hypothesized that the increasing use of piperacillin/tazobactam and other agents with relatively enhanced anti-enterococcal activity (ie, piperacillin, ampicillin/sulbactam, and ampicillin) has been associated with increased or unchanged rates of VRE in some hospitals. DESIGN: We retrospectively evaluated the correlation between hospital antibiotic use (defined daily doses per 10,000 patient-days of care) and incidence of stool or non-stool VRE isolation. We assessed whether a high or increasing proportion of use of beta-lactam agents with relatively enhanced versus minimal (ie, third-generation cephalosporins and ticarcillin/clavulanate) anti-enterococcal activity would prevent increased VRE. SETTING: Four academic medical centers. RESULTS: With the increasing use of piperacillin/tazobactam, the use of beta-lactam agents with enhanced activity against enterococci surpassed the combined use of third-generation cephalosporins and ticarcillin/clavulanate in each hospital. In one hospital, the incidence of VRE was positively correlated with the use of piperacillin/tazobactam or beta-lactam agents with enhanced anti-enterococcal activity (P < .0001). The incidence of VRE rose steadily in another hospital despite relatively high use of beta-lactam agents with enhanced versus minimal anti-enterococcal activity. A negative correlation between VRE and piperacillin/tazobactam or beta-lactam agents with enhanced anti-enterococcal activity was observed in one hospital, but this correlation was not statistically significant. CONCLUSION: Increasing the hospital use of piperacillin/tazobactam and other beta-lactams with relatively enhanced anti-enterococcal activity may not be an effective control measure for VRE.

Academic Medical Centers↗

PubMed2004

Effect of parenteral fluoroquinolone administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract.

We examined the effect of subcutaneous fluoroquinolone antibiotic administration on persistence and density of vancomycin-resistant Enterococcus faecium stool colonization in mice. Levofloxacin and ciprofloxacin did not promote colonization in comparison to saline controls, whereas moxifloxacin and gatifloxacin promoted persistent overgrowth in a dose-dependent fashion.

Amino Acid Sequence↗

PubMed2004

Orally administered targeted recombinant Beta-lactamase prevents ampicillin-induced selective pressure on the gut microbiota: a novel approach to reducing antimicrobial resistance.

Antibiotics that are excreted into the intestinal tract promote antibiotic resistance by exerting selective pressure on the gut microbiota. Using a beagle dog model, we show that an orally administered targeted recombinant beta-lactamase enzyme eliminates the portion of parenteral ampicillin that is excreted into the small intestine, preventing ampicillin-induced changes to the fecal microbiota without affecting ampicillin levels in serum. In dogs receiving ampicillin, significant disruption of the fecal microbiota and the emergence of ampicillin-resistant Escherichia coli and TEM genes were observed, whereas in dogs treated with ampicillin in combination with an oral beta-lactamase, these did not occur. These results suggest a new strategy for reducing antimicrobial resistance in humans.

Administration, Oral↗

PubMed2004

Efficacy of oral ramoplanin for inhibition of intestinal colonization by vancomycin-resistant enterococci in mice.

Ramoplanin is a glycolipodepsipeptide antibiotic with activity against gram-positive bacteria that is in clinical trials for prevention of vancomycin-resistant Enterococcus (VRE) bloodstream infections and treatment of Clostridium difficile diarrhea. Orally administered ramoplanin suppresses VRE intestinal colonization, but recurrences after discontinuation of treatment have frequently been observed. We used a mouse model to examine the efficacy of ramoplanin for inhibition of VRE colonization and evaluated the etiology of recurrences of colonization. Eight days of treatment with ramoplanin (100 microg/ml) in drinking water suppressed VRE to undetectable levels, but 100% of mice developed recurrent colonization; a higher dose of 500 microg/ml in water was associated with recurrent colonization in 50% of mice. Two of eight (25%) mice treated with the 100-microg/ml dose of ramoplanin had low levels of VRE in their cecal tissues on day 8 despite undetectable levels in stool and cecal contents. Mice that received prior ramoplanin treatment did not develop VRE overgrowth when challenged with 10(7) CFU of oral VRE 1, 2, or 4 days later. In communal cages, rapid cross-transmission and overgrowth of VRE was observed among clindamycin-treated mice; ramoplanin treatment effectively suppressed VRE overgrowth in such communal cages. Ramoplanin treatment promoted increased density of indigenous Enterobacteriaceae and overgrowth of an exogenously administered Klebsiella pneumoniae isolate. These results demonstrate the efficacy of ramoplanin for inhibition of VRE colonization and suggest that some recurrences occur due to reexpansion of organisms that persist within the lining of the colon. Ramoplanin treatment may be associated with overgrowth of gram-negative bacilli.

Administration, Oral↗

PubMed2003

Oral administration of beta-lactamase preserves colonization resistance of piperacillin-treated mice.

We hypothesized that orally administered, recombinant class A beta-lactamase would inactivate the portion of parenteral piperacillin excreted into the intestinal tract, preserving colonization resistance of mice against nosocomial pathogens. Subcutaneous piperacillin or piperacillin plus oral beta-lactamase were administered 24 and 12 h before orogastric inoculation of piperacillin-resistant pathogens. Oral administration of beta-lactamase reduced piperacillin-associated alteration of the indigenous microflora and prevented overgrowth of pathogens.

Animals↗

PubMed2003

Coexistence of vancomycin-resistant enterococci and Staphylococcus aureus in the intestinal tracts of hospitalized patients.

The potential for transfer of vancomycin-resistance genes from enterococci to Staphylococcus aureus exists when these organisms share an ecologic niche. We performed an 8-month prospective study to determine the frequency at which S. aureus and vancomycin-resistant enterococci (VRE) coexist in the intestinal tracts of VRE-colonized patients and evaluated whether antianaerobic antibiotic therapy promoted increased density of S. aureus colonization. Of 37 patients colonized with vancomycin-resistant Enterococcus faecium, 23 (62%) had S. aureus recovered from stool specimens and 20 (87%) had methicillin-resistant strains. There was no significant difference in the mean density (+/- standard deviation) of S. aureus during versus > or =1 month after discontinuation of antianaerobic antibiotic therapy (5.1+/-1.5 vs. 4.7+/-1.6 log10 colony-forming units per gram of stool; P=.34). No S. aureus isolates were resistant to vancomycin. S. aureus and VRE often coexist in the intestinal tract, providing a potential reservoir for the emergence of vancomycin-resistant S. aureus isolates.

Aged↗

PubMed2003

Unnecessary use of antimicrobials in hospitalized patients: current patterns of misuse with an emphasis on the antianaerobic spectrum of activity.

BACKGROUND: Unnecessary use of antimicrobials contributes to the emergence and dissemination of antimicrobial-resistant nosocomial pathogens in part through elimination of normal anaerobic bacterial flora that inhibit overgrowth of pathogenic microorganisms. METHODS: A prospective observational study was conducted in a 650-bed, university-affiliated hospital. All adult nonintensive care inpatients for whom new antimicrobials were prescribed during a 2-week period were monitored throughout their hospitalization. We examined how often antimicrobials, in particular those with antianaerobic activity, were used unnecessarily. The reasons for unnecessary therapy were assessed and common patterns of unnecessary use were identified. RESULTS: A total of 1941 antimicrobial days of therapy were prescribed for 129 patients. A total of 576 (30%) of the 1941 days of therapy were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for longer than recommended durations (192 days of therapy), administration of antimicrobials for noninfectious or nonbacterial syndromes (187 days of therapy), and treatment of colonizing or contaminating microorganisms (94 days of therapy). Antianaerobic agents accounted for 203 (35%) of the 576 unnecessary antimicrobial days of therapy, and these agents were also frequently prescribed (98 days of therapy) when equally efficacious alternative regimens with minimal antianaerobic activity were available. CONCLUSIONS: In our institution, hospitalized patients frequently received unnecessary antimicrobial therapy, and antianaerobic agents were often prescribed when this spectrum of activity was not indicated.

Anti-Bacterial Agents↗

PubMed2003

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↗

PubMed2003

Cefotaxime-resistant bacteria colonizing older people admitted to an acute care hospital.

OBJECTIVES: To determine the frequency of fecal colonization by cefotaxime-resistant gram-negative bacilli in older patients living in the community and in long-term care facilities (LTCFs) admitted to an acute care hospital. DESIGN: Case-control, point prevalence study. SETTING: Hospital. PARTICIPANTS: One hundred forty-three patients aged 65 and older. MEASUREMENTS: Rectal swab cultures, antibiotic drug sensitivity, beta lactamase isolation, and clonal identity. RESULTS: Of the 190 surveillance cultures obtained from 143 patients, 26 cefotaxime-resistant gram-negative isolates from 22 patients were recovered. The prevalence rate of cefotaxime-resistant isolates on admission was 13.3% (19/143). A logistic regression model using cefotaxime colonization as the dependent variable found that multiple comorbidities, admission to a surgical service, and having a diagnosis of infection on presentation and a transfusion history were factors associated with the presence of colonization. These four clinical items accurately classified 74% of patients colonized. Antibiotic use and nursing home residence were not associated with the presence of colonization by cefotaxime-resistant organisms. Twelve of the cefotaxime-resistant isolates (46%) were identified as Pseudomonas aeruginosa, and 14 (54%) were other gram-negative bacilli. In six of the 14 isolates that were not P. aeruginosa (36%), it was possible to demonstrate the presence of an AmpC beta-lactamase related to the CMY-2 beta-lactamase, a plasmid-borne cephalosporinase. CONCLUSION: These data raise awareness that there are community- and LTCF-dwelling older patients colonized with gram-negative enteric bacilli resistant to third-generation cephalosporins on admission to the hospital. The "reservoir of resistant bacteria" in older people is no longer confined to LTCFs.

Aged↗

PubMed2003

Role of fecal incontinence in contamination of the environment with vancomycin-resistant enterococci.

BACKGROUND: We tested the hypothesis that patients with vancomycin-resistant Enterococcus (VRE) stool colonization who are continent of feces contaminate the environment less frequently than patients who are colonized and incontinent. METHODS: We prospectively examined the frequency of environmental VRE contamination in the rooms of 15 patients who were continent and 15 who were incontinent and VRE-colonized. Broth-enrichment cultures of bed rails, bedside table, and call buttons were performed at baseline, and 2 and 5 days after environmental disinfection. The numbers of VRE colonies isolated after directly plating environmental swabs onto agar were compared for the continent and incontinent groups. RESULTS: The percentages of patients with 1 or more positive environmental cultures for VRE were not significantly different for the groups of patients who were continent and incontinent at baseline (60% vs 73%, P =.45) or 2 days after disinfection (60% vs 80%, P =.24). The numbers of VRE colonies isolated by direct plating were not significantly different for the continent and incontinent groups (P =.42). CONCLUSIONS: Environmental contamination occurs frequently in the rooms of patients who are continent, and those who are incontinent and VRE-colonized. Our findings suggest that similar infection control measures should be implemented for patients who are continent and incontinent.

Chi-Square Distribution↗

PubMed2003

Clostridium difficile infection and concurrent vancomycin-resistant Enterococcus stool colonization in a health care worker: case report and review of the literature.

Clostridium Difficile diarrhea was noted in a previously healthy health care worker from the study institution after receiving oral clindamycin therapy; the worker also had vancomycin-resistant Enterococcus stool colonization. Health care workers should be aware that antibiotic therapy may place them at increased risk for colonization and infection with nosocomial pathogens such as Clostridium difficile and vancomycin-resistant Enterococcus.

Adult↗

PubMed2003

Colonization and infection with multiple nosocomial pathogens among patients colonized with vancomycin-resistant Enterococcus.

OBJECTIVE: To test the hypothesis that patients colonized with vancomycin-resistant Enterococcus (VRE) have a higher frequency of colonization or infection with other nosocomial pathogens than do patients who are not colonized with VRE. DESIGN: A rectal swab culture survey was conducted to determine the point-prevalence of stool colonization with ceftazidime-resistant gram-negative bacilli in hospitalized patients with or without VRE stool colonization. For a 6-month period, the frequency of Clostridium difficile diarrhea and isolation of antibiotic-resistant (ie, ceftazidime-, piperacillin/tazobactam-, levofloxacin-, or trimethoprim/sulfamethoxazole-resistant) gram-negative bacilli, methicillin-resistant Staphylococcus aureus (MRSA), and non-albicans Candida species from clinical specimens other than stool was examined. SETTING: A Department of Veterans Affairs medical center. PATIENTS: All patients hospitalized in the acute care facility and one nursing home unit during a 1-week period in February 2001. RESULTS: VRE-colonized patients had a higher point-prevalence of rectal colonization with ceftazidime-resistant gram-negative bacilli than did patients not colonized with VRE (17% vs 4%; P = .026). During a 6-month period,the VRE-colonized patients were more likely to have Clostridium difficile-associated diarrhea (26% vs 2%; P = .001), MRSA infection (17% vs 4%; P = .017), or colonization or infection with gram-negative bacilli resistant to 4 different antibiotics. CONCLUSION: VRE-colonized patients in our institution have a higher frequency of colonization or infection with other nosocomial pathogens than do patients who are not colonized with VRE. This suggests that isolation measures implemented to control VRE could help limit the dissemination of other, coexisting pathogens.

Aged↗