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Curtis J Donskey

Publications and source records attributed to Curtis J Donskey.

At least 19 recordsLinked to original sources

Use of Whole Genome Sequencing to Investigate the Risk for Transmission of Clostridioides difficile From Prior Room Occupants: A Single-Center Study.

BACKGROUND: Admission to a room previously occupied by a patient with Clostridioides difficile infection (CDI) has been identified as a risk factor for CDI. However, previous studies have not included molecular typing to definitively link healthcare-associated CDI (HA-CDI) cases to prior room occupants. METHODS: In a hospital and affiliated long-term care facility, we conducted a 1-year cohort study to determine if exposure to a room previously occupied by a CDI patient and/or with environmental contamination after cleaning and disinfection in the past 3 months was associated with an increased risk of HA-CDI. Multivariable logistic regression was used to assess risk factors for HA-CDI. Whole genome sequencing was used to determine the relatedness of HA-CDI isolates and isolates from prior CDI cases or environmental surfaces. RESULTS: Of 5,746 admitted patients, 55 were diagnosed with HA-CDI. Exposure to a room previously occupied by a CDI patient and/or with a positive post-discharge culture was not associated with an increased risk of HA-CDI (adjusted odds ratio 1.15, 95% confidence interval 0.65-1.98; P=0.62). None of the 21 HA-CDI patients with prior room-level exposures were infected with isolates genomically related to isolates from prior room occupants with CDI or from room surfaces. Five HA-CDI cases were linked to prior CDI patients or environmental isolates on the same ward or without ward-level exposure. CONCLUSION: Despite frequent exposure to rooms previously occupied by CDI patients or contaminated with C. difficile, no HA-CDI cases were linked to prior room exposures in a facility using sporicidal disinfectants in CDI rooms.

Clostridioides difficile↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients.

BACKGROUND AND OBJECTIVE: Antianaerobic antibiotic therapy promotes persistent high-density growth of vancomycin-resistant enterococci (VRE) in the stool of colonized patients. We tested the hypothesis that antibiotic regimens with potent antianaerobic activity promote overgrowth of coexisting antibiotic-resistant, gram-negative bacilli in the stool of VRE-colonized patients. DESIGN: Eight-month prospective study examining the effect of antibiotic therapy on the stool density of gram-negative bacilli resistant to ceftazidime, ciprofloxacin, or piperacillin/tazobactam. SETTING: A Department of Veterans Affairs medical center including an acute care hospital and nursing home. PATIENTS: All VRE-colonized patients with at least 3 stool samples available for analysis. RESULTS: One-hundred forty stool samples were obtained from 37 study patients. Forty-nine (61%) of 80 stool samples obtained during therapy with an antianaerobic regimen were positive for an antibiotic-resistant, gram-negative bacillus, where-as only 14 (23%) of 60 samples obtained 4 or more weeks after completion of such therapy were positive (P < .001). Twenty-four (65%) of the 37 patients had one or more stool cultures positive for a gram-negative bacillus resistant to ciprofloxacin, ceftazidime, or piperacillin/tazobactam. The density of these organisms was higher during therapy with antianaerobic regimens than in the absence of such therapy for at least 2 weeks (mean +/- standard deviation, 5.6 +/- 1.4 and 3.9 +/- 0.71 log10 organisms/g; P < .001). CONCLUSION: Limiting the use of antianaerobic antibiotics in VRE-colonized patients may reduce the density of colonization with coexisting antibiotic-resistant, gram-negative bacilli.

Adult↗

Effect of parenteral antibiotic administration on establishment of intestinal colonization in mice by Klebsiella pneumoniae strains producing extended-spectrum beta-lactamases.

A mouse model was used to test the hypothesis that antibiotics with activity against anaerobes promote overgrowth of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strains in stool. Subcutaneous clindamycin consistently promoted establishment of high-density colonization, whereas piperacillin-tazobactam, ceftriaxone, and ceftazidime promoted colonization only when a large inoculum and/or more resistant strain was administered.

Animals↗