Containment of COVID-19 outbreak at a veterans affairs community living center.

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. Both HCP likely worked on the floor while pre-symptomatic. When one HCP reported a cough to the secondary (employee) screening clinic, she was erroneously advised to work. Protocols to limit the risk for HCP to import COVID-19 were reinforced with Community Living Center staff as well as with personnel in secondary screening. Further, the CLC implemented an expanded screening tool that assessed residents for typical and atypical symptoms of COVID-19. No further cases of COVID-19 were detected on the CLC floor in the subsequent 6 weeks. Swift recognition and response helped contain the outbreak and prevent further COVID-19 infections among other residents and staff.

The Impact of Natural Transformation on the Acquisition of Antibiotic Resistance Determinants.

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.org/10.1128/mBio.02631-21) delineate the unsuspected extent and circumstances under which natural transformation as a mechanism of intraspecies and interspecies exchange of genetic material occurs in Acinetobacter spp. This study offers key insights into how this notorious pathogen may have accelerated the development of its MDR phenotype via an unexpectedly robust and unnervingly casual approach to the acquisition of antibiotic resistance determinants through natural transformation.

A Comparison of Cefazolin Versus Ceftriaxone for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia in a Tertiary Care VA Medical Center.

BACKGROUND: Cefazolin and ceftriaxone are frequently used to treat methicillin-susceptible Staphylococcus aureus (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. METHODS: We conducted a retrospective cohort study of Veteran patients with MSSA bacteremia who received ≥14 days of cefazolin or ceftriaxone between 2009 and 2014. Rates of treatment failure were compared between both groups. Treatment failure was defined as therapy extension, incomplete therapy, unplanned oral suppressive therapy, relapse of infection, or hospital admission or surgery within 90 days. RESULTS: Out of 71 patients, 38 received treatment with cefazolin and 33 with ceftriaxone. The overall rate of treatment failure was 40.8%, with significantly more failures among patients receiving ceftriaxone (54.5% versus 28.9%; P = .029). Factors associated with treatment failure included longer duration of parenteral therapy, heart failure, and treatment in an external skilled nursing facility as compared with treatment in the Department of Veterans Affairs attached Community Living Center. CONCLUSIONS: Ceftriaxone had a higher rate of treatment failure than cefazolin for the treatment of MSSA bacteremia in a Veteran population. Potential reasons for this could include the higher protein binding of ceftriaxone, ultimately resulting in lower serum concentrations of free drug, or other unknown factors. Further studies are warranted to confirm these results.

Perception vs Reality: Methicillin-Resistant Staphylococcus aureus Carriage Among Healthcare Workers at a Veterans Affairs Medical Center.

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. However, 100 (62%) of 162 workers completing an associated survey believed themselves to be colonized, revealing a knowledge deficit about methicillin-resistant Staphylococcus aureus epidemiology. Infect. Control Hosp. Epidemiol. 2015;37(1):110-112.

Metallo-ß-lactamase-producing bacteroides species can shield other members of the gut microbiota from antibiotics.

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, ß-lactamase-producing Bacteroides strains raised the minimum bactericidal concentration of ceftriaxone required to kill a susceptible Escherichia coli strain (mean change, <0.25 to 29 mg/liter; P = 0.009); incubation with ceftriaxone-resistant but non-ß-lactamase-producing Bacteroides strains had no effect. The production of ß-lactamase by common members of the intestinal microbiota (Bacteroides) can protect susceptible fellow commensals from ß-lactams.

Gastrointestinal colonization with a cephalosporinase-producing bacteroides species preserves colonization resistance against vancomycin-resistant enterococcus and Clostridium difficile in cephalosporin-treated mice.

Antibiotics that are excreted into the intestinal tract may disrupt the indigenous intestinal microbiota and promote colonization by health care-associated pathogens. ß-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 ß-lactamase enzymes that inactivate ß-lactam antibiotics. We hypothesized that prior establishment of intestinal colonization with a ß-lactamase-producing anaerobe might prevent these adverse effects of ß-lactam antibiotics, by inactivating the portion of antibiotic that is excreted into the intestinal tract. Here, mice with a previously abolished microbiota received either oral normal saline or an oral cephalosporinase-producing strain of Bacteroides thetaiotaomicron for 3 days. Mice then received 3 days of subcutaneous ceftriaxone, followed by either oral administration of vancomycin-resistant Enterococcus (VRE) or sacrifice and assessment of in vitro growth of epidemic and nonepidemic strains of Clostridium difficile in murine cecal contents. Stool concentrations of VRE and ceftriaxone were measured, cecal levels of C. difficile 24 h after incubation were quantified, and denaturing gradient gel electrophoresis (DGGE) of microbial 16S rRNA genes was performed to evaluate the antibiotic effect on the microbiota. The results demonstrated that establishment of prior colonization with a ß-lactamase-producing intestinal anaerobe inactivated intraintestinal ceftriaxone during treatment with this antibiotic, allowed recovery of the normal microbiota despite systemic ceftriaxone, and prevented overgrowth with VRE and epidemic and nonepidemic strains of C. difficile in mice. These findings describe a novel probiotic strategy to potentially prevent pathogen colonization in hospitalized patients.

Contamination of hands with methicillin-resistant Staphylococcus aureus after contact with environmental surfaces and after contact with the skin of colonized patients.

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.

Occurrence of skin and environmental contamination with methicillin-resistant Staphylococcus aureus before results of polymerase chain reaction at hospital admission become available.

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. METHODS: We conducted a 6-week prospective study of patients who were identified by use of polymerase chain reaction (PCR) at hospital admission as having nasal MRSA colonization. Skin and environmental contamination was assessed within hours of completion of PCR screening. RESULTS: There were 116 patients identified by PCR screening as having nasal MRSA colonization during the period from mid-April to May 2008, of whom 83 (72%) were enrolled in our study. Overall, MRSA was detected on the skin of 38 (51%) of 74 patients and in the environment of 37 (45%) of 83 patients. Of 83 environmental culture samples, 63 (76%) were obtained within 7 hours after PCR results became available, and 73 (88%) were obtained before wards were notified of PCR results. Of the 83 MRSA-colonized patients, 15 (18%) had contaminated their environment 25 hours after admission, and 29 (35%) had contaminated their environment 33 hours after admission. Thirty-two (39%) of the 83 patients had roommates, 13 (41%) of whom contaminated their environment. The median interval from admission to PCR result was 20 hours, and the median interval from PCR result to notification was 23 hours. An increased quantity of MRSA cultured from a nasal sample was significantly associated with contamination. CONCLUSIONS: Before any contact precautions can be implemented, newly identified MRSA carriers frequently have contaminated their environment with MRSA and have contamination of commonly examined skin sites. In hospitals that perform active surveillance, strategies are needed to minimize delays in screening or to preemptively identify patients at high risk for disseminating MRSA.

Skin and environmental contamination with methicillin-resistant Staphylococcus aureus among carriers identified clinically versus through active surveillance.

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. aureus carriage was identified clinically, which suggests that strategies to limit transmission must address colonized patients, as well as infected patients.

Orally administered beta-lactamase enzymes represent a novel strategy to prevent colonization by Clostridium difficile.

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. difficile in mice. METHODS: Subcutaneous ampicillin, subcutaneous piperacillin or either of these plus oral beta-lactamase or either of these plus tazobactam-inactivated oral beta-lactamase were administered to mice 24 and 12 h prior to harvest of caecal contents. Contents were inoculated with one of four strains of C. difficile, and growth and toxin production were assessed after 24 h of incubation under anaerobic conditions. To assess changes in stool microbiota, denaturing gradient gel electrophoresis (DGGE) of PCR-amplified ribosomal RNA genes was performed. RESULTS: Mice treated with ampicillin, piperacillin or either of these plus tazobactam-inactivated oral beta-lactamase developed high-density colonization with C. difficile, whereas those treated with ampicillin or piperacillin plus the beta-lactamase did not. DGGE demonstrated that antibiotic treatment resulted in significant alteration of the indigenous stool microbiota, whereas antibiotic plus beta-lactamase treatment did not. CONCLUSIONS: Administration of oral recombinant beta-lactamase preserved the colonic microbiota of mice during parenteral beta-lactam antibiotic treatment and prevented the overgrowth of and toxin production by C. difficile in caecal contents. Oral beta-lactamase therapy may represent a novel approach towards preventing C. difficile infections in healthcare settings.

Emergence and acquisition of fluoroquinolone-resistant gram-negative bacilli in the intestinal tracts of mice treated with fluoroquinolone antimicrobial agents.

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.

Effect of carbapenem administration on establishment of intestinal colonization by vancomycin-resistant enterococci and Klebsiella pneumoniae in mice.

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.

Suppression of gastric acid production by proton pump inhibitor treatment facilitates colonization of the large intestine by vancomycin-resistant Enterococcus spp. and Klebsiella pneumoniae in clindamycin-treated mice.

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.

Effect of a selective decontamination of the digestive tract regimen including parenteral cefepime on establishment of intestinal colonization with vancomycin-resistant Enterococcus spp. and Klebsiella pneumoniae in mice.

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.

Effects of daptomycin, linezolid, and vancomycin on establishment of intestinal colonization with vancomycin-resistant enterococci and extended-spectrum-beta-lactamase-producing Klebsiella pneumoniae in mice.

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.

Mechanisms by which anaerobic microbiota inhibit the establishment in mice of intestinal colonization by vancomycin-resistant Enterococcus.

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. After orogastric inoculation of VRE, clindamycin-treated mice acquired high concentrations of VRE within the mucus layer, whereas saline-treated mice did not. These results suggest that colonic microbiota inhibit VRE by producing inhibitory substances or conditions rather than by depleting nutrients. The colonic mucus layer provides a potential niche for growth of VRE.

Effect of parenteral antibiotic administration on establishment of intestinal colonization by Candida glabrata in adult mice.

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. glabrata colonization.