Megan Duster

Antibiotic resistance in non-major metropolitan skilled nursing facilities: prevalence and interfacility variation.

Skilled nursing facilities (SNFs) represent ideal environments for the emergence and spread of antibiotic resistance.1 Studies have found that residents in Veterans Administration (VA) SNFs2,3 and non-VA SNFs in major metropolitan areas4,5 are frequently colonized with antibiotic-resistant bacteria (ARB). The extent to which residents of non-urban SNFs are colonized with ARB remains poorly understood. Intrinsic differences in patient populations, referral patterns as well as other contextual factors may fuel very different patterns of antibiotic resistance in non-urban SNFs. Our group recently completed a longitudinal study to document patterns of antibiotic resistance in several SNFs located in non-urban counties of South Central Wisconsin. Herein, we present the colonization results of surveillance cultures performed at the inception of the study cohort in 2008–2009. The University of Wisconsin’s Institutional Review Board approved this study. A potential pool of 39 SNFs (size, ≥ 60 beds) located in 9 South Central Wisconsin counties was constituted from a directory of licensed facilities maintained by the State of Wisconsin. A randomly assigned number was used to determine the order in which facilities were approached by the research team. Six of the first 10 facilities approached agreed to participate. Variables describing characteristics of the facility and resident population were constructed from annual data collected during the state survey process as well as data collected from medical records of subjects at study entry. Residents of participating SNFs over the age of 18, including those with cognitive impairment, were eligible to participate. After obtaining written informed consent, multi-anatomical screening for colonization with methicillin-resistant Staphylococcus aureus (MRSA) and fluoroquinolone-resistant gram-negative bacteria (FQRGNB) was performed. Cultures of nares, skin of the axilla and groin, and perianal skin (or stool) were obtained from all subjects to detect MRSA colonization. Additional cultures of wounds, the insertion site of non-urinary indwelling medical devices, and urine collected from indwelling urinary device were obtained, when applicable. The same body sites, exclusive of nares and axilla/groin, were sampled to detect FQRGNB colonization. MRSA specimens were enriched in trypticase soy broth supplemented with 6.5% NaCl for 24 hours before plating onto selective media -- Mannitol Salt agar (Remel, Lenexa, KS) containing 4 µg/mL of cefoxitin. FQRGNB specimens were plated directly onto MacConkey agar (Remel, Lenexa, KS) containing 4 µg/mL of ciprofloxacin. All plates were incubated aerobically for 48 hours at 37°C and were identified to the species level using standard techniques. Cefoxitin and ciprofloxacin resistance was confirmed using the Kirby Bauer disk diffusion method. Point estimates and 95% confidence intervals of the proportion of residents colonized with MRSA and FQRGNB were calculated. Pearson chi-square tests were performed to identify if a significant difference in the proportion of subjects colonized with MRSA and FQRGNB across study locations was present. When applicable, visual inspection of confidence limits was performed to identify facility pairs accounting for those differences. The characteristics of the participating facilities, including characteristics of participating subjects in aggregate, are presented in Table 1. 449 of the 851 (53%) residents in the 6 participating SNFs were screened at baseline. An equal proportion of subjects were colonized with MRSA (22.3%; 95% CI 13.7 – 30.9%) and FQRGNB (21.3%; 95% CI 13.3 – 29.3%). Approximately 5% of participating subjects were co-colonized with MRSA and FQRGNB (95% CI 2.8 – 7.1%). Overall, 38.7% (95% CI 32.9 – 44.5%) of subjects screened were colonized with either MRSA and/or FQRGNB. Table 1 Facility Characteristics and Prevalence of Antibiotic-Resistant Bacteria for 6 Skilled Nursing Facilities in South Central Wisconsin. Significant variation in the proportion of subjects colonized with MRSA (Pearson chi-square = 14.6, P = 0.012) and FQRGNB (Pearson chi-square = 13.2, P = 0.022) was identified across the 6 facilities. Significant differences in the prevalence of MRSA were identified between Facility #3 (13.0%) and Facility #4 (33.7%). Significant differences in the prevalence of FQRGNB were identified between Facility #2 (29.1%) and Facility #6 (11.3%). The characteristics of facilities with the highest prevalence of MRSA or FQRGNB were not qualitatively different from facilities with a lower prevalence of MRSA or FQRGNB (Table 1). The generalizeability of our findings may be limited by the method in which study facilities were selected. Our study facilities, while representative of non-urban SNFs that cater to long-term stay residents requiring nursing services of low complexity, may not be representative of urban SNFs that provide a more complex level of nursing care.6 Nevertheless, the prevalence of MRSA in facilities in our study are not substantively different from those recently described for SNFs in a highly urbanized county in California.7 Comparable data on the prevalence of FQRGNB in other SNFs are not available. However, recently published studies describing sharp increases in the proportion of clinical isolates obtained from residents of Northeastern SNFs that were resistant to fluoroquinolone antibiotics8 as well as a high prevalence of FQRGNB colonization among SNF residents with an indwelling medical device9 support the generalizeability of our findings. In combination, these data suggest that a post-fluoroquinolone era has begun to emerge in U.S. SNFs. Few studies have attempted to measure the variation in antibiotic resistance across SNFs within the same geographic region.7,10 The twofold variation in FQRGNB prevalence and threefold variation in MRSA prevalence seen among SNFs in our study raise questions that require further study. Specifically, is variation being driven by differences in referral patterns, intra-facility antibiotic prescribing, intra-facility adherence to transmission-based precautions or some combination thereof? Pursuing the answers to these questions will be important for developing and implementing interventions to reduce the regional spread of antibiotic resistance. In summary, our study affirms the notion that residents of SNFs are commonly colonized with MRSA and FQRGNB, even in non-urban facilities that provide relatively low complexity of nursing care. Considerable variation in the prevalence of MRSA and FQRGNB in SNFs in the same geographic region exists. The explanations for this degree of inter-facility variation remain poorly understood and deserve further study.

Feasibility of Oral Prenatal Probiotics against Maternal Group B Streptococcus Vaginal and Rectal Colonization

OBJECTIVE To examine the effect of an oral prenatal probiotic on group B Streptococcus (GBS) colonization and to demonstrate the feasibility of a larger randomized controlled trial. DESIGN This pilot study was an open-label, two-group quasi-experiment. SETTING An urban central city nurse-midwifery and wellness center serving a diverse population. PARTICIPANTS Ten pregnant participants received the oral probiotic (Florajen3) taken once daily, and 10 participants served as controls. METHODS A questionnaire on dietary practices, vaginal cleansing, sexual history, and symptoms and GBS colony count samples were taken at 28-, 32-, and 36-weeks gestation. RESULTS Participants in the probiotic group reported no adverse events or minor side effects; one half reported improved gastrointestinal symptoms. Although two women in each group had positive qualitative prenatal GBS cultures at 36 weeks, the probiotic group participants had lower quantitative GBS colony counts. The eight GBS negative averaged 90% probiotic adherence compared with two GBS positive women who averaged 68%. Yogurt ingestion was inversely related (p = .02) to GBS colonization. CONCLUSIONS Prenatal probiotic therapy has the potential to reduce GBS colonization. The potential of the probiotic intervention appears to be linked to daily adherence. A controlled clinical trial with a larger, adequately powered sample is feasible and justified.

Clostridium difficile in a children's hospital: Assessment of environmental contamination

Clostridium difficile infection (CDI) is the most frequent infectious cause of health care-associated diarrhea. Three cases of CDI, in children age 2, 3, and 14 years, occurred in the hematology/oncology ward of our childrens hospital over 48 hours. We aimed to assess environmental contamination with C difficile in the shared areas of this unit, and to determine whether person-to-person transmission occurred. C difficile was recovered from 5 of 18 samples (28%). We compared C difficile isolated from each patient and the environment using pulsed-field gel electrophoresis, and found that none of the patient strains matched any of the others, and that none matched any strains recovered from the environment, suggesting that person-to-person transmission had not occurred. We found that C difficile was prevalent in the environment throughout shared areas of the childrens hospital unit. Molecular typing to identify mechanisms of transmission is useful for devising appropriate interventions.

Comparison of Pulsed-Gel Electrophoresis and a Commercial Repetitive-Element PCR Method for Assessment of Methicillin-Resistant Staphylococcus aureus Clustering in Different Health Care Facilities

ABSTRACT Pulsed-field gel electrophoresis (PFGE) is a common method used to type methicillin-resistant Staphylococcus aureus (MRSA) in nosocomial investigations and epidemiological studies but is time-consuming and methodologically challenging. We compared typing results obtained using a commercial repetitive-element PCR (rep-PCR) system with PFGE in a sample of 86 unique MRSA isolates recovered from subjects in an academic referral hospital and two nursing homes in the same geographic region. Both methods reliably assigned isolates to the same Centers for Disease Control and Prevention (CDC) pulsotype. PFGE was significantly more discriminatory (Simpsons index of diversity, 0.92 at the 95% strain similarity threshold) than the commercial rep-PCR system (Simpsons index of diversity, 0.58). The global (adjusted Rand coefficient, 0.10) and directional congruence (adjusted Wallace coefficientrepPCR→PFGE = 0.06; adjusted Wallace coefficientPFGE→repPCR = 0.52) between the two methods was low. MRSA strains recovered from study nursing homes that were clonal when typed by the commercial rep-PCR method were frequently noted to be genetically distinct when typed using PFGE. These data suggest that the commercial rep-PCR has less utility than PFGE in small-scale epidemiological assessments of MRSA in health care settings.

Impact of Probiotics for Reducing Infections in Veterans (IMPROVE): Study protocol for a double-blind, randomized controlled trial to reduce carriage of Staphylococcus aureus

BACKGROUND Staphylococcus aureus (S. aureus) is an organism of great public health importance, causing 20,000 deaths annually. Decolonization of patients with S. aureus may prevent infections, yet current options are limited to antimicrobials that promote antibiotic resistance and can cause adverse side effects. Probiotics have potential to reduce colonization of pathogenic bacteria, representing a promising alternative for S. aureus decolonization, but thus far lack rigorous evaluation. METHODS Potential subjects were recruited from inpatient and outpatient settings within a VA medical center and screened for S. aureus gastrointestinal (GI) or extra-GI colonization using swabs at multiple body sites. Positive, eligible, consenting participants were stratified by colonization site and randomized in a 1:1 ratio to 4-weeks of daily placebo or Lactobacillus rhamnosus (L. rhamnosus) HN001 probiotic treatment. Blood and stool samples, and treatment adherence reports were collected from each subject throughout the study, along with a final set of swabs at study completion to detect S. aureus carriage. The outcomes of this study are GI or extra-GI carriage by S. aureus at the end of 4weeks of therapy, change in phagocytic activity of polymorphonuclear cells from pre-intervention to post-intervention, and symptomatic S. aureus infection at any site during the study period. CONCLUSION 114 participants have been recruited for this study. Analysis of outcomes is underway. This is the first clinical trial to examine the efficacy of L. rhamnosus HN001 for decolonization of S. aureus, and investigates the mechanism by which L. rhamnosus HN001 mediates its effect on S. aureus colonization. ClinicalTrials.govIdentifier NCT01321606.

Probiotics for Clostridium difficile infection in adults (PICO): Study protocol for a double-blind, randomized controlled trial.

BACKGROUND Clostridium difficile is a pathogen of rapidly increasing public health importance. An estimated quarter of a million Clostridium difficile infections (CDI) occur in the United States annually, at a resultant cost of 14,000 deaths and 1 billion dollars. Clostridium difficile related deaths have risen 400% over the last decade, and current standard antibiotic treatments are only 75 to 85% successful. Besides increasing the risk of antibiotic resistance and side effects, these treatments are very expensive. The most vulnerable population for Clostridium difficile is older adults, who make up approximately half of the cases, but account for 90% of the related deaths. Probiotics may have potential as adjunctive therapeutic agents for CDIs, however, current data is limited. METHODS This pilot study is a single-site, randomized, placebo-controlled, double-blind, phase two clinical trial. The trial primarily evaluates the effect of four weeks of probiotic therapy in addition to standard of care on Clostridium difficile diarrhea duration and recurrence. Secondary outcomes include effect on fecal cytokines, fecal lactoferrin, and Clostridium difficile toxin density in stool, as well as patient functional status. DISCUSSION This pilot study will determine the feasibility and effect size to conduct larger randomized controlled trials of probiotic interventions in patients with CDI, to determine the impact of probiotics on the symptoms of CDI. ClinicalTrials.gov Identifier: NCT01680874.

Macrolide and Clindamycin Resistance in Group A Streptococci Isolated from Children With Pharyngitis.

Group A streptococcus (GAS) is responsible for 15%–30% of cases of acute pharyngitis in children. Macrolides such as azithromycin have become popular for treating GAS pharyngitis. We report macrolide resistance rates in a primary care setting in our geographic area over the past 5 years and discuss the implications of resistance in making treatment decisions. Throat swabs were collected from children with pharyngitis from May 2011 to May 2015 in a primary care setting in Madison, Wisconsin. Susceptibility testing was performed for erythromycin and clindamycin using the Kirby–Bauer disk diffusion method. GAS was identified on 143 throat cultures. Overall, 15% of GAS isolates demonstrated nonsusceptibility for both clindamycin and erythromycin. Inducible resistance (positive D-test) was detected in 17 isolates (12%). The rate of detection of nonsusceptibility in each year of the study did not change over time. Azithromycin should only be used for patients with pharyngitis and substantial manifestations of penicillin hypersensitivity and when used, susceptibility testing should always be performed.

A randomized controlled trial of probiotics for Clostridium difficile infection in adults (PICO)

Background Clostridium difficile is the most common cause of hospital-acquired infections, responsible for >450000 infections annually in the USA. Probiotics provide a promising, well-tolerated adjunct therapy to standard C. difficile infection (CDI) treatment regimens, but there is a paucity of data regarding their effectiveness for the treatment of an initial CDI. Objectives We conducted a pilot randomized controlled trial of 33 participants from February 2013 to February 2015 to determine the feasibility and health outcomes of adjunct probiotic use in patients with an initial mild to moderate CDI. Methods The intervention was a 28 day, once-daily course of a four-strain oral probiotic capsule containing Lactobacillus acidophilus NCFM, Lactobacillus paracasei Lpc-37, Bifidobacterium lactis Bi-07 and B. lactis Bl-04. The control placebo was identical in taste and appearance. Registered at clinicaltrials.gov: trial registration number = NCT01680874. Results Probiotic adjunct therapy was associated with a significant improvement in diarrhoea outcomes. The primary duration of diarrhoea outcome (0.0 versus 1.0 days; P = 0.039) and two exploratory outcomes, total diarrhoea days (3.5 versus 12.0 days; P = 0.005) and rate of diarrhoea (0.1 versus 0.3 days of diarrhoea/stool diary days submitted; P = 0.009), all decreased in participants with probiotic use compared with placebo. There was no significant difference in the rate of CDI recurrence or functional improvement over time between treatment groups. Conclusions Probiotics are a promising adjunct therapy for treatment of an initial CDI and should be further explored in a larger randomized controlled trial.

Risk of Clostridium difficile Infection in Hematology-Oncology Patients Colonized With Toxigenic C. difficile

The prevalence of colonization with toxigenic Clostridium difficile among patients with hematological malignancies and/or bone marrow transplant at admission to a 566-bed academic medical care center was 9.3%, and 13.3% of colonized patients developed symptomatic disease during hospitalization. This population may benefit from targeted C. difficile infection control interventions. Infect Control Hosp Epidemiol 2017;38:718-720.

Vancomycin-resistant Enterococcus co-colonization rates with methicillin-resistant Staphylococcus aureus and Clostridium difficile in critically ill veterans

A prospective study was conducted to identify risk factors for vancomycin-resistant Enterococcus, including co-colonization with methicillin-resistant Staphylococcus aureus and Clostridium difficile infection in patients admitted to the intensive care unit in 2 Veterans Affairs facilities. Methicillin-resistant Staphylococcus aureus and Clostridium difficile infection co-colonization were significant risk factors for vancomycin-resistant Enterococcus colonization. Further studies are needed to identify measures for preventing co-colonization of these major organisms in veterans.