Publications by authors named "Usha Stiefel"

Asymptomatic and pre-symptomatic staff and residents likely contribute to widespread transmission of COVID-19 in long-term care settings. Here, we describe the successful containment of a COVID-19 outbreak on one floor of a 163-bed Veterans Affairs (VA) Community Living Center (CLC). Testing using nasopharyngeal swabs with a rapid turn-around-time identified 3 of 28 (11%) residents and 2 of 41 (5%) healthcare personnel (HCP) with COVID-19.

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Carbapenem and multidrug-resistant (MDR) Acinetobacter baumannii leads the World Health Organization's list of priority pathogens and represents an unmet medical need. Understanding the mechanisms underpinning the acquisition of antibiotic resistance in this pathogen is fundamental to the development of novel therapeutics as well as to infection prevention and antibiotic stewardship strategies designed to limit its spread. In their investigation, "Interbacterial Transfer of Carbapenem Resistance and Large Antibiotic Resistance Islands by Natural Transformation in Pathogenic Acinetobacter," Anne-Sophie Godeux and colleagues (mBio 13:e0263121, 2022, https://doi.

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Background: Cefazolin and ceftriaxone are frequently used to treat methicillin-susceptible (MSSA) bacteremia, especially in the realm of outpatient parenteral antimicrobial therapy. Both antimicrobials have been associated with favorable clinical outcomes for mixed MSSA infections. However, limited published data exist specifically comparing the use of these agents for the treatment of MSSA bacteremia.

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In a prevalence study of 209 healthcare workers, 18 (8.6%) and 13 (6.2%) carried methicillin-resistant Staphylococcus aureus in their nares or on their hands, respectively.

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Antibiotics disrupt the intestinal microbiota, rendering patients vulnerable to colonization by exogenous pathogens. Intermicrobial interactions may attenuate this effect. Incubation with ceftriaxone-resistant, ccrA-positive, β-lactamase-producing Bacteroides strains raised the minimum bactericidal concentration of ceftriaxone required to kill a susceptible Escherichia coli strain (mean change, <0.

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Antibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. β-Lactam, or penicillin-type, antibiotics are among the most widely utilized antibiotics worldwide and may also adversely affect the microbiota. Many bacteria are capable, however, of producing β-lactamase enzymes that inactivate β-lactam antibiotics.

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In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission.

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Background: Active surveillance to detect patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) is increasingly practiced in healthcare settings. However, inpatients may already become sources of transmission before appropriate precautions are implemented.

Objective: To examine the frequency of MRSA contamination of commonly touched skin and environmental surfaces before patient carriage status became known.

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In a prospective study involving 115 patients with methicillin-resistant Staphylococcus aureus nares carriage, we found that skin and environmental contamination with methicillin-resistant S. aureus was as likely among individuals whose S. aureus carriage was identified only through active surveillance as it was among those individuals whose S.

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Objectives: Antibiotics that are excreted into the intestinal tract and that disrupt the indigenous microbiota may promote infection by Clostridium difficile. We previously demonstrated that oral administration of a proteolysis-resistant, recombinant class A beta-lactamase inactivates ampicillin or piperacillin excreted into the small intestine during parenteral treatment. We hypothesized that oral administration of this beta-lactamase in conjunction with parenteral ampicillin or piperacillin would preserve the colonic microbiota, thus preventing the overgrowth of and toxin production by C.

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After mice received orogastric administration of a fluoroquinolone-resistant Klebsiella pneumoniae strain, subcutaneous treatment with ciprofloxacin, levofloxacin, and moxifloxacin promoted persistent low-density colonization in 10% to 40% of the mice, whereas treatment with clindamycin consistently promoted high-density colonization. No emergence of fluoroquinolone-resistant gram-negative bacilli was detected in the mice during or after treatment with the fluoroquinolone antimicrobial agents.

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In a mouse model, ertapenem inhibited the anaerobic intestinal microflora and promoted overgrowth of enterococci, whereas imipenem-cilastatin had no effect on the indigenous microflora. Ertapenem, but not imipenem-cilastatin, promoted modest overgrowth of vancomycin-resistant enterococci when exposure occurred during treatment. Neither agent promoted colonization with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae.

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Proton pump inhibitor treatment of clindamycin-treated mice elevated the gastric pH and facilitated the establishment of colonization of the large intestine by vancomycin-resistant Enterococcus spp. (75 to 80%, versus 20 to 25% for saline-treated controls) and Klebsiella pneumoniae (90%, versus 30% for saline-treated controls). These findings demonstrate a mechanism by which proton pump inhibitor therapy could contribute to the dissemination of nosocomial pathogens.

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In mice, a selective decontamination of the digestive tract regimen consisting of orogastric tobramycin, polymyxin E, and amphotericin B in combination with subcutaneous cefepime inhibited gram-negative bacilli, including Klebsiella pneumoniae, and did not promote vancomycin-resistant Enterococcus spp. (VRE) colonization. However, concurrent administration of subcutaneous ampicillin-sulbactam resulted in promotion of VRE.

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In mice, vancomycin and linezolid treatment disrupted the anaerobic intestinal microflora, based on denaturing gradient gel electrophoresis analysis, and promoted colonization by Klebsiella pneumoniae and vancomycin-resistant enterococci. However, the effects varied depending on dose and duration of treatment. Daptomycin treatment did not disrupt the anaerobic microflora or promote either pathogen.

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We used a mouse model to test the hypothesis that anaerobic microbiota in the colon inhibit the establishment of vancomycin-resistant enterococci (VRE) colonization by depleting nutrients within cecal contents and limiting the association of VRE with the mucus layer. Anaerobic growth of VRE was assessed in cecal contents and cecal mucus of mice that had received treatment with subcutaneous clindamycin or saline. VRE grew to high concentrations in cecal contents of clindamycin-treated mice and in cecal mucus of both groups but not in cecal contents of saline-treated mice, unless the cecal contents were autoclaved or converted into sterile filtrates.

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We examined the effect of antibiotic treatment on establishment of intestinal colonization by Candida glabrata in adult mice. Subcutaneous ceftriaxone, piperacillin-tazobactam, clindamycin, and metronidazole promoted increased density of stool colonization, whereas cefepime, levofloxacin, and aztreonam did not. These findings suggest that antibiotics that inhibit intestinal anaerobes promote C.

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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.

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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.

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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.

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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.

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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.

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