Nebulizers, a standard treatment device for patients with chronic 

 including asthma, are susceptible to major bacteria pathogen contamination, as well as microbiomes attributed to their surrounding environments.

American Society of Microbiology (ASM) 2021 World Microbe Forum

 this week, define concerning risks of bacteria infection associated with the common inhalation therapy among a growing population of American patients.

A team of University of Tennessee investigators, led by Clifford S. Swanson, of the Department of Civil and Environmental Engineering, sought to determine colonized bacteria trends among nebulizer devices, as well as the potential sources of such contamination.

As they noted, previous research into the matter showed various pathogens have colonized nebulizers over a relatively short period of patient use—but without associated increased risk of contamination over time of use.

“The use of nebulizer devices are ubiquitous with the treatment of respiratory illnesses, where medicines are delivered to deep within the respiratory tract via aerosolization,” Swanson and colleagues wrote. “A major concern with these devices, however, is the potential contamination by microbial pathogens as it would elevate the risk of nosocomial infections for the patient.”

Their assessment included adult in-patients admitted to the University of Tennessee Medical Center, who used jet nebulizers for respiratory diseases. The team collected 2 nebulizers, each within 24-48 hours of use, from in-patients to be treated as replicates for each patient.

One nebulizer was collected for use in bacterial abundance quantification via heterotrophic plate counts (HCPs), while the other was used for future 16S rRNA amplicon sequencing.

Taxonomy of the average collected nebulizer showed the major Phyla included 

—both of which consist of environmental bacteria and potential pathogens. The 10 top taxonomic groups observed by investigators indicated the most abundant bacteria typically includes 

. The groups include major environmental and human microbiome bacteria.

Source tracking software helped indicate that indoor environments comprised more than 40% contribution to contamination of nebulizers, followed by significantly lower rates of skin, oral, and gut source contributions.

Investigators concluded in their assessment of bacterial nebulizer device contamination that major bacteria could include potential pathogens included 

“It also revealed that there was a significant amount of microbiome that could be attributed to the surrounding environment instead of humans,” investigators concluded. “This study revealed the potential concerns that some of the colonizing bacteria pose with these nebulizer devices.”

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ASM Microbe  Conference

New ASM data show indoor environments are associated with quick and frequent pathogen contamination of the common respiratory device.

Nebulizers Linked to Environmental Bacterial Contamination

 this week showed county-level factors for heightened risk of 

 mortality included increased rates of asthmatic patients, Black persons, and persons aged ≥65 years old in the community.

The findings—which elucidate how county-level factors including total hospitals, insurance rates, and mobile home population rates were associated with fatalities in the first wave of US COVID-19 outbreaks last year—may help provide unique public health intervention targets prior to future outbreaks.

during ASM 2021 regarding the findings, study author Jess Millar, graduate research assistant at the University of Michigan’s departments of Computational Medicine & Bioinformatics and Epidemiology, discussed their contribution to regional-level research and discussion around health inequality relative to the pandemic.

As she noted, previous research has established social determinants of health involved in the unequal impact of COVID-19 on Black and African-American communities—including structural racism’s effect on their access to financial resources, reliance on public transportation, housing instability, and reliance on low-paying retail jobs.

“Our approach considered several other variables that might help explain the effect, but were either non-signficant—such as household crowding, percentage of households without vehicle, and county land area—or were correlated with percentages of Black and African-Americans—such as percentage of single-parent households and percentage living in poverty—further emphasizing the role of systemic racism in COVID-19 case fatality rate,” Millar said.

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An interview with a study author on unique associations between county infrastructures and COVID-19 fatality rates.

Older Age, Asthma, Black Population Influence County-Level COVID-19 Fatality

detection was associated with an approximate 81% sensitivity and 100% specificity compared to standard PCR testing.

, a team of Virginia-based investigators reported the capability of the Abbott BinaxNOW COVID-19 antigen test—marketed for its ability to provide assay results in approximately 15 minutes for SARS-CoV-2 infection.

Led by Alexandra L. Bryson, PhD, of the Department of Pathology at the Virginia Commonwealth University Health System, the real-world comparison of PCR versus rapid antigen testing showed the latter missed an approximate 18% of COVID-19 cases among those who tested positive on the former assay.

The US Food and Drug Administration (FDA) originally granted Emergency Use Authorization (EUA) to a litany of COVID-19 diagnostic tests based on what Bryson and colleagues described as “limited validation data,” a factor which is particularly concern for use of antigen-based assays.

“Rapid, antigen-based assays present as an enticing test method because of their quick turnaround time, low cost, and ease of use,” investigators wrote, “however, antigen-based assays are known to have inferior sensitivity and specificity compared to PCR-based assays.”

The team conducted a prospective, paired-specimen trial to assess the sensitivity and specificity of the BinaxNOW antigen test versus 2 different PCR tests: the TaqPath COVID-19 Combo Kit from ThermoFisher, or the Cobas SARS-CoV-2 test from Roche.

Their evaluation included 283 patients from the academic medical center, who consented to 2 specimen assays. Nasal swabs collected by a care provider were tested with the BinaxNOW system, then nasopharyngeal swabs from both nostrils were tested by PCR within 24 hours.

Bryson and colleagues observed 60 PCR positive results among the 283 tested patients, versus 233 PCR negative tests. Nearly all (n = 250) patients reported COVID-19 symptoms; just 12 were asymptomatic, and 21 had unknown symptom status.

The rapid COVID-19 antigen test demonstrated 81.7% sensitivity, with 11 false negatives, and 100% specificity. The BinaxNOW system failed to detect all 4 PCR-positive samples with average Ct value greater than 28. It additionally missed 3 strong PCR-positive samples with average Cts of 12, 16, and 18.

The 4 remaining false negatives observed in the antigen samples had Cts ranging from 20 – 26, indicating an observed inaccuracy of the rapid antigen assay in detecting SARS-CoV-2 in patients with greater viral loads.

“This study demonstrates that the BinaxNOW COVID-19 Ag Card misses (approximately) 18% of COVID-19 cases across a wide range of PCR positive Ct values including patients presumed to have high viral loads,” they concluded.

New findings on an available 15-minute test show an approximate 81% sensitivity in detection of SARS-CoV-2.

Rapid COVID-19 Antigen Test Provides Less Sensitivity Than PCR Assay

An available RT-PCR assay has shown capability to detect prevalent UK 

 variant strain B.1.1.7, according to an assessment of 100-plus samples collected in the first half of 2021.

 this week, provide assurance that the ThermoFisher TaqPath COVID-19 RT-PCR assay—granted Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA)—is a device able to assist tracking the more transmissible SARS-CoV-2 variant, originally observed in southeast England in Fall 2020.

Led by Derek Moates, MBS, of the UAB Fungal Reference Lab, Department of Pathology and Laboratory Medicine at the University of Alabama at Birmingham, investigators sought to observe the clinical utility of the RT-PCR assay in detecting B.1.1.7 through remnant nasopharyngeal swab sequencing.

As they noted, identifying SARS-CoV-2 variants of concern and significance require whole genome sequencing (WGS), a process generally hindered by costs, skilled personnel availability, limited resourcing, and time constraints.

“However, once a variant of public health significance is known, targeted RT-PCR assays may enable accurate, high throughput, and cost-effective detection to help guide epidemiologic interventions,” they wrote.

Moates and colleagues conducted testing of symptomatic patients who tested positive for all gene targets except the SARS-CoV-2 spike gene, or “S gene dropout.”

Samples with cycle threshold (Ct) value <30 were sequenced via a WGS panel. Preliminary SARS-CoV-2 variant calls and genome assemblies were obtained via relevant software, as were lineage calls.

The investigators attempted WGS on 79 samples with Ct <30 that also exhibited S gene dropout. They obtained sufficient coverage and read depth for variant calls and genome assembly in 92.5% (n = 111) of 120 overall samples.

Among 3 repeated samples, all maintained success. All 111 (100%) S gene dropout samples successfully read were identified as UK SARS-CoV-2 variant B.1.1.7.

Hands on time and mean time to result per run were 4 hours and 24 hours, respectively.

Moates and colleagues concluded the findings support the use of the ThermoFisher RT-PCR COVID-19 assay for detecting and screening for the B.1.1.7 variant of SARS-CoV-2.

“Although WGS is the gold standard and is essential to identify novel variants, RT-PCR screens for the UK and other known variants of public health significance may enable high throughput and cost-effective variant detection to help guide epidemiologic interventions,” they wrote.

New findings from the ASM 2021 World Microbe Forum suggest the emergency-authorized platform can capably detected the highly transmissible UK-borne variant.

ThermoFisher RT-PCR COVID-19 Test Detects B.1.1.7 Variant

Across the world there are 38 million people living with the 

 (HIV) or Acquired Immunodeficiency Syndrome (AIDS). While numbers are on the decline, 1.7 million people acquired the HIV virus in 2019.

Treating HIV comes with several challenges and barriers, including a high cost of treatment, access to care, retention in care and transition from inpatient to outpatient care.

Contagion recently sat down with Melissa Badowski, PharmD, MPH, a clinical associate professor in the department of pharmacy practice at the University of Illinois at Chicago to discuss the issue of challenges in HIV management

Annual Making a Difference in Infectious Disease Meeting 2021 virtual sessions

“Were very stringent with our medical appointments. If you miss it by 10 or 15 minutes, a lot of patients will get turned away,” Badowski said. “Where in HIV care, it’s just the opposite. We try to remove any barriers; we try to meet the patient where they’re at.”

Patients face many barriers, from the ability to get their medication to being stigmatized from having HIV.

“HIV has been around for a long time, but I still think of it as being stigmatized,” Badowski said. “If we can just reduce the ‘Oh, this is just an infectious disease.’ I think that would help a lot of our patients with reducing that stigma.”

MAD-ID

A discussion on issues surrounding the treatment of HIV with Melissa Badowski, PharmD, MPH.

Challenges in HIV Management and Therapy

When it comes to patient care and the use of antibiotics, antimicrobial stewardship programs are of vital importance. It has been demonstrated that when institutions utilize such programs they see a decrease in not only antibiotic use, but cost and associated infections as well.

However, inappropriate antibiotic use at hospital discharge has been worrying experts, as they often result in regimens that are too long, improperly dosed, or are too broad in spectrum.

Recently, investigators from the Moses H. Cone Memorial Hospital, in collaboration with the Fred Wilson School of Pharmacy at High Point University, conducted research which sought to evaluate discharge antibiotic prescribing and to see if a specific, pharmacist-led intervention could improve appropriate use.

Contagion sat down with Kushal Naik, PharmD, MBA, a pharmacy resident at Moses H. Cone, who presented the research at the 

“The purpose of our research was to figure out a way how we can optimize patient discharge prescribing,” Naik said. “In the hospital, we have a lot of targeted efforts to improve antimicrobial stewardship, but many of these efforts are not carried out for discharge prescriptions.”

The quasi-experimental, pre-post study evaluated 162 patients who were 18 years of age or older and were discharged from the hospital with an oral antibiotic prescription. Two groups were included, a retrospective group evaluated a random sample of patients discharged in February of 2020 and a prospective group included patients discharged between January and April 2021.

Findings showed that of the 162 participants, 86 (53.1%) were discharged on inappropriate antimicrobial therapy, excessive duration being the principal driver. Of the pharmacist led interventions, 37 (66.1%) of 56 were accepted by providers in the intervention period.

“Pharmacists definitely have a large role to play in this field and in the whole sphere of antimicrobial stewardship in general,” Naik said. “Pharmacists, as well as our physician colleagues, are pretty up to date with our guide line recommendations and a pharmacist led intervention like this can continue to foster those guideline directed recommendations to be implemented in all of our patients.”

A conversation on antimicrobial stewardship with Kushal Naik, PharmD, MBA.

How Pharmacist-led Interventions Can Improve Discharge Antibiotic Use

A monoclonal antibody developed for both the treatment and prevention of COVID-19 displayed neutralizing activity against the virus as well as protection against it in animal models.

The monoclonal antibody named ADG2 was “engineered to possess high potency and broad neutralization against SARS-CoV, SARS-CoV-2, and pre-emergent SARS-like-CoVs. ADG20, a half-life extended version of ADG2, is being developed for the prevention and treatment of coronavirus disease (COVID-19)," the investigators wrote. "ADG2 and ADG20 displayed potent neutralizing activity against the original SARS-CoV-2 strain and all known variants of concern and provided significant protection against SARS and COVID-19 in mouse models.” 

The data was presented virtually at the 

“ADG2 displayed potent neutralizing activity against SARS-CoV (IC50 of 4–8 ng/mL) and SARS-CoV-2 (IC50 of ~1 ng/mL) and bound with high affinity to RBDs of 12/13 clade 1 SARS-like-CoVs, with a KDAPP of 0.24–1.12 nM. ADG2 bound to all SARS-CoV-2 variants tested at levels ≥50% of wild-type (WT) SARS-CoV-2; whereas loss of binding (>75% reduced relative to WT) to one or more variants was observed for other clinical mAbs,” the investigators reported. “ADG20 also displayed little to no reduction (<4-fold) in neutralizing activity across 3 variants of concern (P.1, B.1.351, B.1.1.7), with all reaching a plateau at 100% neutralization.”

The company that developed the monoclonal therapy is Adimab. They announced last summer that it had launched Adagio Therapeutics, which is a biotechnology company that will develop a portfolio of anti-coronavirus antibodies as both therapeutics and prophylactics against COVID-19 and future coronaviruses.

In February, Adagio announced it began its phase 1 trial for ADG20. “We are in the unique position of having a monoclonal antibody that binds to and protects against common circulating SARS-CoV-2 variants as well as SARS-related viruses with pandemic potential,” Adagio CEO Tillman Gerngross, said at that time. “This broadly neutralizing activity was intentionally designed into ADG20, as we anticipated the continued emergence of resistance mutations, and we took deliberate steps to engineer ADG20 to maximize its potential to avoid viral escape. This design feature also enables ADG20 to target and neutralize coronaviruses that may emerge in the future.” 

An investigational therapy demonstrated neutralizing antibodies as well as protection against the virus in preclinical trials.

 Monoclonal Antibody Being Developed for Treatment and Prevention of COVID-19, Variants

Healthcare associated infections (HAI) can be a tremendous burden on hospital systems, patients, and clinicians. Within (HAI), rCDI can be a particularly challenging burden having patients deal with the same ongoing health issue. One study looked at the number of hospital admissions of Medicare patients and saw 20% of inpatients had rCDI as the primary diagnosis.

The findings were presented virtually at the 

23rd Annual Making a Difference in Infectious Disease Meeting 2021 virtual sessions

Investigators performed a large retrospective analysis looking at Medicare patient hospital admissions. They looked at Part A Medicare claims from January 2018 to June 2019. They had a total of 43,039 patients with 47,115 CDI-related hospital admissions, and 9472 of these admissions had rCDI.

They studied a variety of factors in 2 groups: CDI-related hospital admissions and non-CDI admissions. They looked at the length of stay (LOS), costs per admission, discharge status, outcomes, and in-hospital mortality.

The results did show differences in each patient group. For example, rCDI admissions resulted in higher inpatient costs than non-rCDI admissions. Investigators also found patients’ LOS was slightly longer for rCDI than non-rCDI admissions: 6.0 (5.7) vs 5.5 (5.1) days.

 spoke to principal investigator Meg Franklin, PharmD, PhD, president of Franklin Pharmaceutical Consulting who provided some insights into the understanding of the analysis including the patient implications and financial burden these challenging infections cost.

A study looked at hospital admissions of Medicare patients and saw a large percentage of recurrent Clostridioides difficile infections (rCDI) as the primary diagnosis.

The Burden of Clostridioides Difficile

 therapy durations have been shown to be just as effective as longer therapy durations for many infections. Shorter durations of therapy have also resulted in fewer adverse events.

Recently, a community hospital added a computerized physician order entry (CPOE) system in the electronic health record, which requires indication, as well as the treatment duration to be documented on all antibiotic orders prior to order submission for pharmacist verification.

Investigators from the North Florida Regional Medical Center set out to determine if the implementation of this system would decrease the duration of therapy in hospitalized patients with bacterial pneumonia.

The retrospective, pretest-posttest, interrupted time series, quasi-experimental study included 138 patients, of which 56 were included in the pre-intervention group and 82 were included in the post-intervention group.

The patients were administered antibiotic therapy ≥ 48 hours for bacterial pneumonia between April 1, 2016, to May 1, 2016, and April 1, 2017, to May 1, 2017. The primary endpoint of the study was the length of therapy for antibiotics prescribed for bacterial pneumonia.

Findings from the study demonstrated that there was no difference found in the outcomes of length of hospital stay, 30-day readmission, in-hospital 30-day mortality, or incidence of in-hospital C. difficile infection.

Additionally, the median length of antibiotic therapy in the pre-intervention group was 4.4 days (IQR 2.9-5.9) and duration in the post-intervention group was 4.5 days (IQR: 3.5-5.2).

“Implementation of mandatory indication and default stop dates did not impact duration of inpatient antibiotic therapy for bacterial pneumonia patients. Requiring stop dates also did not result in harm,” the authors wrote. “Unmeasurable impacts of the required documentation includes enabling clinical evaluation of antibiotic orders, assessment for appropriateness of antibiotic selection by indication, and dose adjustments based on indication.”

No difference was observed in any of the outcomes and there was no impact on the duration of therapy.

Mandatory Stop Dates, Indication Documentation Do Not Impact Length of Antibiotic Therapy

Although 10% of patients report having an allergy to an antibiotic, many are still able to take the medication or one similar. Attempts to initiate early, optimal therapy should be made in patients with documented antibiotic allergies to avoid inferior clinical outcomes, higher risk of adverse events, and increased length of hospital stay.

Two strategies which can be implemented in patients with a reported allergy are graded dose challenge (GDC) and desensitization (DSENS). Graded dose challenge assesses a patient’s ability to tolerate a therapy or a related one, while desensitization provides the ability to administer a drug (or related drug) despite a convincing IgE-mediated allergy.

However, ordering and administration operational and safety challenges have the potential to limit the use of these 2 strategies.

Recently, investigators from Atrium Health, in collaboration with the University of North Carolina Eshelman School of Pharmacy, have conducted an evaluation to determine the safety and efficacy of protocols for GDC and DSENS.

The single health-system, multicenter, retrospective evaluation included 76 participants who were receiving a GDC or DSENS for an antibiotic between February 1, 2019, and September 30, 2020. The primary objective of this study was to determine the proportion of patients undergoing GDC and DSENS who tolerated a full dose of the target antibiotic.

Of the 76 patients in the evaluation, 58 met inclusion criteria, 50 for GDC and 8 for DSENS.

Findings from the evaluation showed that of the 50 patients receiving GDC, 45 (90%) tolerated a full antibiotic dose and 44 (88%) tolerated a full course. The 8 patients receiving DSENS tolerated the procedure and full target antibiotic course.

Additionally, 5 of the patients required rescues medications, 4 in the GDC group and 1 in the DSENS group, but none of them had any prolonged complications.

“Used under the guidance of ASP pharmacists or ID physicians, antibiotic GDC and DSENS are safe and effective tools to optimize therapy in patients who report an IgE-mediated antibiotic allergy,” the authors wrote.

GDC and DSENS were both seen to be safe and effective tools to optimize therapy in the study participants.

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