28 NICUs participating in a quality improvement collaborative targeting early-onset sepsis antibiotic use.

OBJECTIVE: There is widespread overuse of antibiotics in neonatal intensive care units (NICUs). The objective of this study was to safely reduce antibiotic use in participating NICUs by targeting early-onset sepsis (EOS) management. STUDY DESIGN: Twenty-eight NICUs participated in this statewide multicenter antibiotic stewardship quality improvement collaborative. The primary aim was to reduce the total monthly mean antibiotic utilization rate (AUR) by 25% in participant NICUs. RESULT: Aggregate AUR was reduced by 15.3% (p < 0.001). There was a wide range in improvement among participant NICUs. There were no increases in EOS rates or nosocomial infection rates related to the intervention. CONCLUSION: Participation in this multicenter NICU antibiotic stewardship collaborative targeting EOS was associated with an aggregate reduction in antibiotic use. This study informs efforts aimed at sustaining improvements in NICU AURs.

Characterization of COVID-19 Vaccine Hesitancy Among Essential Workforce Members of a Large Safety Net Urban Medical Center.

OBJECTIVES: Vaccine hesitancy among essential workers remains a significant public health challenge. We examined psychological constructs of perceived susceptibility, threat, and self-efficacy and their associations with COVID-19 vaccine hesitancy among a racially and ethnically diverse essential workforce population. METHODS: We performed a cross-sectional survey of essential workers from September-December 2020 at a large Los Angeles safety-net medical center as part of a program offering free COVID-19 serology testing. Program participants completed a standardized survey at the time of phlebotomy. Hierarchical logistic regression was utilized to determine factors independently associated with vaccine hesitancy. RESULTS: Among 1327 persons who had serology testing, 1235 (93%) completed the survey. Of these, 958 (78%) were healthcare workers. Based on expressed intent, 22% were vaccine-hesitant 78% were vaccine acceptors. In our multivariate model, vaccine hesitancy was associated with female gender [aOR = 2.09; 95% CI (1.44-3.05)], African American race [aOR = 4.32; (2.16-8.62)], LatinX ethnicity [aOR = 2.47; 95% CI (1.51-4.05)] and history of not/sometimes receiving influenza vaccination [aOR = 4.39; 95% CI (2.98-6.48)]. Compared to nurses, vaccine hesitancy was lower among physicians [aOR = 0.09; 95% CI (0.04-0.23)], non-nursing/non-physician healthcare workers [aOR = 0.55; 95% CI (0.33-0.92)], and non-healthcare care workers [aOR = 0.53; 95% CI (0.36-0.78)]. CONCLUSIONS: Among a racially/ethnically diverse group of safety net medical center essential workers, COVID-19 vaccine hesitancy was associated with racial/ethnic minority groups, employment type, and prior influenza vaccination hesitancy. Interestingly, we found no association with the Health Belief Model construct measures of perceived susceptibility, threat, and self-efficacy. Psychological constructs not assessed may be drivers of vaccine hesitancy in our population.

Blood culture procedures and practices in the neonatal intensive care unit: A survey of a large multicenter collaborative in California.

OBJECTIVE: To describe variation in blood culture practices in the neonatal intensive care unit (NICU). DESIGN: Survey of neonatal practitioners involved with blood culturing and NICU-level policy development. PARTICIPANTS: We included 28 NICUs in a large antimicrobial stewardship quality improvement program through the California Perinatal Quality Care Collaborative. METHODS: Web-based survey of bedside blood culture practices and NICU- and laboratory-level practices. We evaluated adherence to recommended practices. RESULTS: Most NICUs did not have a procedural competency (54%), did not document the sample volume (75%), did not receive a culture contamination report (57%), and/or did not require reporting to the provider if <1 mL blood was obtained (64%). The skin asepsis procedure varied across NICUs. Only 71% had a written procedure, but ≥86% changed the needle and disinfected the bottle top prior to inoculation. More than one-fifth of NICUs draw a culture from an intravascular device only (if present). Of 13 modifiable practices related to culture and contamination, NICUs with nurse practitioners more frequently adopted >50% of practices, compared to units without (92% vs 50% of units; P < .02). CONCLUSIONS: In the NICU setting, recommended practices for blood culturing were not routinely performed.

Chlorhexidine and Mupirocin for Clearance of Methicillin-Resistant Staphylococcus aureus Colonization After Hospital Discharge: A Secondary Analysis of the Changing Lives by Eradicating Antibiotic Resistance Trial.

BACKGROUND: The CLEAR Trial demonstrated that a multisite body decolonization regimen reduced post-discharge infection and hospitalization in methicillin-resistant Staphylococcus aureus (MRSA) carriers. Here, we describe decolonization efficacy. METHODS: We performed a large, multicenter, randomized clinical trial of MRSA decolonization among adult patients after hospital discharge with MRSA infection or colonization. Participants were randomized 1:1 to either MRSA prevention education or education plus decolonization with topical chlorhexidine, oral chlorhexidine, and nasal mupirocin. Participants were swabbed in the nares, throat, axilla/groin, and wound (if applicable) at baseline and 1, 3, 6, and 9 months after randomization. The primary outcomes of this study are follow-up colonization differences between groups. RESULTS: Among 2121 participants, 1058 were randomized to decolonization. By 1 month, MRSA colonization was lower in the decolonization group compared with the education-only group (odds ration [OR] = 0.44; 95% confidence interval [CI], .36-.54; P ≤ .001). A similar magnitude of reduction was seen in the nares (OR = 0.34; 95% CI, .27-.42; P < .001), throat (OR = 0.55; 95% CI, .42-.73; P < .001), and axilla/groin (OR = 0.57; 95% CI, .43-.75; P < .001). These differences persisted through month 9 except at the wound site, which had a relatively small sample size. Higher regimen adherence was associated with lower MRSA colonization (P ≤ .01). CONCLUSIONS: In a randomized, clinical trial, a repeated post-discharge decolonization regimen for MRSA carriers reduced MRSA colonization overall and at multiple body sites. Higher treatment adherence was associated with greater reductions in MRSA colonization.

The antibiogram: key considerations for its development and utilization.

The antibiogram is an essential resource for institutions to track changes in antimicrobial resistance and to guide empirical antimicrobial therapy. In this Viewpoint, data and examples from literature are presented that suggest institutions have not completely adopted the standardized approach in developing antibiograms, as variations in the development methodologies of antibiograms exist despite consensus guidelines (M39) published by CLSI. We emphasize developing antibiograms in line with the M39 recommendations will help ensure that they are accurate, reliable and valid, and highlight that understanding the limitations of antibiogram data is critical to ensuring appropriate interpretation and application to clinical decision-making. We also stress the importance of easy accessibility and education on antibiogram use, to allow for prescribers to select the most optimal empirical treatment regimens and propose the creation of an abbreviated antibiogram for frontline users. Multidisciplinary antimicrobial stewardship programmes are vital to accomplishing these goals.

Detection of carbapenem resistant enterobacteriace from fomite surfaces.

Accurately identifying carbapenem resistant enterobacteriace (CRE) from fomites is critical for infection control practices, research, and assessing patient risk. We compared a commercial CRE agar intended for patient use with a modified MacConkey agar. We found that our modified MacConkey agar was more selective at identifying CRE from environmental sources.

Cost-benefit analysis comparing trough, two-level AUC and Bayesian AUC dosing for vancomycin.

OBJECTIVES: Area under the time-concentration curve (AUC) -guided dosing provides better estimates of exposure than vancomycin trough concentrations. Though clinical benefits have been reported, the costs of AUC-guided dosing are uncertain. The objective of this study was to quantify the costs of single-sample Bayesian or two-sample AUC strategies versus trough-guided dosing. METHODS: A cost-benefit analysis from the institutional perspective was conducted using a decision tree to model the probabilities and costs of acute kidney injury (AKI) associated with vancomycin administered over 48 hours up to 21+ days. Costs included vancomycin concentrations, Bayesian software and AKI hospitalization costs, and probabilities were obtained from primary literature. Robustness was assessed via both one-way and probabilistic sensitivity analyses. RESULTS: In the base-case model, two-sample AUC versus trough dosing saved an average of US$ 846 per patient encounter, and single-sample Bayesian AUC versus trough dosing saved an average of US$ 2065 per patient encounter. This translates into annual cost-savings of US$ 846 810 and US$ 2 065 720 for two-sample and single-sample Bayesian methods versus trough dosing, respectively, assuming 1000 vancomycin-treated patients per year. Assuming a budget of US$ 100 000 per year for Bayesian software, an institution would need to treat ≥41 patients with vancomycin for at least 48 hours to break even. CONCLUSIONS: There are significant institutional cost benefits using two-sample AUC or single-sample Bayesian methods over trough dosing, even after accounting for the annual costs of Bayesian programs. The potential to decrease rates of AKI, improve clinical outcomes and reduce costs to the institution strongly warrants consideration of improved dosing methods for vancomycin.

Decolonization to Reduce Postdischarge Infection Risk among MRSA Carriers.

BACKGROUND: Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge. METHODS: We conducted a multicenter, randomized, controlled trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence). RESULTS: In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval [CI], 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants. CONCLUSIONS: Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234 .).

Early onset sepsis calculator-based management of newborns exposed to maternal intrapartum fever: a cost benefit analysis.

OBJECTIVE: To determine potential net monetary benefit of an early onset sepsis calculator-based approach for management of neonates exposed to maternal intrapartum fever, compared to existing guidelines. STUDY DESIGN: We performed a cost-benefit analysis comparing two management approaches for newborns >34 weeks gestational age exposed to maternal intrapartum fever. Probabilities of sepsis and meningitis, consequences of infection and antibiotic use, direct medical costs, and indirect costs for long-term disability and mortality were considered. RESULTS: A calculator-based approach resulted in a net monetary benefit of $3998 per infant with a 60% likelihood of net benefit in probabilistic sensitivity analysis. Our model predicted a 67% decrease in antibiotic use in the calculator arm. The absolute difference for all adverse clinical outcomes between approaches was ≤0.6%. CONCLUSIONS: Compared to existing guidelines, a calculator-based approach for newborns exposed to maternal intrapartum fever yields a robust net monetary benefit, largely by preventing unnecessary antibiotic treatment.

The Hyr1 protein from the fungus Candida albicans is a cross kingdom immunotherapeutic target for Acinetobacter bacterial infection.

Different pathogens share similar medical settings and rely on similar virulence strategies to cause infections. We have previously applied 3-D computational modeling and bioinformatics to discover novel antigens that target more than one human pathogen. Active and passive immunization with the recombinant N-terminus of Candida albicans Hyr1 (rHyr1p-N) protect mice against lethal candidemia. Here we determine that Hyr1p shares homology with cell surface proteins of the multidrug resistant Gram negative bacterium, Acinetobacter baumannii including hemagglutinin (FhaB) and outer membrane protein A (OmpA). The A. baumannii OmpA binds to C. albicans Hyr1p, leading to a mixed species biofilm. Deletion of HYR1, or blocking of Hyr1p using polyclonal antibodies, significantly reduce A. baumannii binding to C. albicans hyphae. Furthermore, active vaccination with rHyr1p-N or passive immunization with polyclonal antibodies raised against specific peptide motifs of rHyr1p-N markedly improve survival of diabetic or neutropenic mice infected with A. baumannii bacteremia or pneumonia. Antibody raised against one particular peptide of the rHyr1p-N sequence (peptide 5) confers majority of the protection through blocking A. baumannii invasion of host cells and inducing death of the bacterium by a putative iron starvation mechanism. Anti-Hyr1 peptide 5 antibodies also mitigate A. baumannii /C. albicans mixed biofilm formation in vitro. Consistent with our bioinformatic analysis and structural modeling of Hyr1p, anti-Hyr1p peptide 5 antibodies bound to A. baumannii FhaB, OmpA, and an outer membrane siderophore binding protein. Our studies highlight the concept of cross-kingdom vaccine protection against high priority human pathogens such as A. baumannii and C. albicans that share similar ecological niches in immunocompromised patients.

Adjunctive Corticosteroid Therapy in the Treatment of Coccidioidal Meningitis.

Coccidioidal meningitis (CM) has high morbidity, and adjunctive measures to improve outcomes are needed. Using an established multicenter retrospective cohort study of CM (N = 221), we found that patients receiving adjunctive corticosteroids had a significant reduction in secondary cerebrovascular events (P = .0049). Those with CM-associated cerebrovascular events (8%) may benefit from short-term corticosteroids.

Prevalence of and Factors Associated With Multidrug Resistant Organism (MDRO) Colonization in 3 Nursing Homes.

Nursing home residents are at risk for acquiring and transmitting MDROs. A serial point-prevalence study of 605 residents in 3 facilities using random sampling found MDRO colonization in 45% of residents: methicillin-resistant Staphylococcus aureus (MRSA, 26%); extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL, 17%); vancomycin-resistant Enterococcus spp. (VRE, 16%); carbapenem-resistant Enterobacteriaceae (CRE, 1%). MDRO colonization was associated with history of MDRO, care needs, incontinence, and catheters. Infect Control Hosp Epidemiol 2016;1485-1488.

Molecular epidemiology and characterization of multiple drug-resistant (MDR) clinical isolates of Acinetobacter baumannii.

OBJECTIVES: The aim of this study was to identify the genetic relatedness of multiple drug-resistant (MDR) Acinetobacter baumannii clinical isolates recovered from a hospital in Los Angeles. METHODS: Twenty-one MDR A. baumannii isolates were collected and their antibiotic susceptibilities determined according to Clinical and Laboratory Standards Institute guidelines. Genes coding for antibiotic resistance were identified by PCR, and their identities were confirmed by DNA sequencing. Clonal relationships were studied by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). RESULTS: MDR consistently correlated with the presence of oxacillinases, mostly in the form of the plasmid-mediated OXA-23 enzyme, which was detected in 12 (57.1%) isolates. GES-type carbapenemases were found in 20 (95.2%) strains, AAC in all 21 (100%) strains, and PER in seven (33.3%) strains, and ISAba1 was detected in 16 (76.2%) isolates. The association between ISAba1 and resistance genes confirms insertion elements as a source of ß-lactamase production. Of the 21 clinical isolates, five were found to be related to sequence type 1 (ST1) and 16 to ST2, as analyzed by MLST. PFGE demonstrated that the majority of clinical isolates were highly related (>85%). CONCLUSIONS: This study supports a more complete understanding of genotyping of antibiotic resistance for better assessment of MDR strain transmission.

Clinicocytopathologic correlation in an atypical presentation of lymphadenopathy with review of literature.

OBJECTIVES: To present a clinicocytopathologic correlation of an atypical case of cat scratch disease (CSD) involving retroperitoneal lymph nodes, with emphasis on communication between service teams for managing lymphadenopathy of unknown origin. We consider clinical and cytologic differential diagnoses and review the literature on atypical cases of CSD, with emphasis on abdominal presentation and cytologic findings. METHODS: Clinical services met with the cytology service to review clinical and pathologic features. Literature was reviewed via PubMed search (Harbor-UCLA subscriptions). Immunohistochemistry and Steiner silver stains were performed by Harbor-UCLA Department of Pathology. Enzyme-linked immunosorbent assay IgG and IgM Bartonella henselae titers were carried out by Quest Nichols Institute. RESULTS: Fine-needle aspirate Diff-Quik and Papanicolaou smears and H&E-stained cell block showed abundant histiocytes, monocytoid B cells, and numerous neutrophils associated with necrosis corresponding to a late stage of CSD infection. Silver stain was positive for clumps of pleomorphic organisms. IgM and IgG antibody titers were elevated. CONCLUSIONS: The cytologic findings of CSD in an atypical abdominal presentation are similar to those of a classic presentation. Laboratory workup for atypical CSD should include at least two other modalities aside from cytomorphologic features. Close clinical and cytologic correlation avoided potentially unnecessary and harmful surgery and enabled timely treatment.

Body site Staphylococcus aureus colonization among maintenance hemodialysis patients.

BACKGROUND: Patients on maintenance hemodialysis therapy are at high risk for health care-associated infections. Staphylococcus aureus is a common cause of health care-associated infections among maintenance hemodialysis patients. It is established that S. aureus colonization is associated with an increased risk for subsequent infection in this population. There is an increasing number of reports that extranasal S. aureus colonization is more common than previously believed and in certain body sites even more common than nasal colonization. There are few data describing extranasal colonization among maintenance hemodialysis patients. METHODS: We surveyed 100 patients at 3 body sites (anterior nares, oropharynx, and inguinal region) for S. aureus colonization. Participants were also administered a standardized survey to assess risk factors for S. aureus colonization. RESULTS: We found that 42% (95% CI 32-52) of patients were S. aureus colonized in >1 body site. Extranasal colonization was found among 32% (95% CI 23-41). There were trends suggestive of an association between S. aureus colonization and younger age (OR 0.97, 95% CI 0.94-1.001, p = 0.06) and not having been hospitalized in the previous 12 months (OR 0.44, 95% CI 0.19-1.06, p = 0.14). CONCLUSION: Extranasal S. aureus colonization is common among maintenance hemodialysis patients with a prevalence of approximately one third. Future S. aureus decolonization efforts may need to consider not just nasal decolonization but also decolonization of the skin and oropharynx.

Routine CSF analysis in coccidioidomycosis is not required.

Although routinely done, there has been no evaluation of the utility of performing routine cerebrospinal fluid (CSF) examination in patients with active coccidioidomycosis and high complement fixation (IgG) antibody titers or other risk factors for disseminated infection. In our review 100% of patients diagnosed with coccidioidal meningitis had at least one sign or symptom consistent with infection of the central nervous system, headache was present in 100% of those with meningitis, while no patients without signs/symptoms of CNS infection were found to have coccidioidal meningitis, irrespective of antibody titers or other risk factors. Thus routine lumbar puncture may be unnecessary for patients with coccidioidomycosis who lack suggestive clinical symptoms.