Ken reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and provided and managed pharmacy care and drug information services. He regularly contributes to Contagion Live, HCP Live, Neurology Live, and Pain Medicine News.

Kenneth Bender, PharmD, MA

Vaccination was associated with dramatic reductions in both asymptomatic and symptomatic COVID-19 cases among health care personnel (HCP), despite a surge in infected patients during the 2020-2021 Winter.

 at the University of California Irvine (UCI) Health, the sole academic medical center in Orange County, California, was conducted when this sixth largest US county was confronting among the highest infection rates in the Country.Investigators determined that daily HCP cases of COVID-19 fell 55% (from 18 to 8) 1 week after the 2nd vaccination dose.There was an 84% reduction (3 cases) after 2 weeks and 94% (1 case) 3 weeks after full vaccination.

"HCP cases declined when our hospital was still in full surge with an active mobile field hospital and several outpatient areas commandeered for inpatient intensive care unit and non-intensive care unit beds," the investigators reported.

The cases of COVID-19 among over 10,000 HCP in the study were tracked before and after 2-dose vaccination with a Pfizer or Moderna mRNA vaccine through daily screening for elevated temperature and for CDC-defined COVID-19 symptoms; with rapid nasopharyngeal testing if fever or symptoms were present.In addition, asymptomatic bilateral nares testing was provided weekly to HCP randomly selected from invited volunteers.

WIth invited rather than mandated vaccination, 58% of HCP received a first dose within 2 weeks, and 70% within 4 weeks.Twenty-five percent of HCP were invited to receive weekly asymptomatic testing, with approximately 15% of these (500) participating.

The investigators noted that most HCP with COVID-19 who were identified through asymptomatic test (81% (34 of 42) within the 21-week study period reported having symptoms at the posttest interview.Many had dismissed their symptoms as common ailments at the time, but recognized them as COVID-19 in hindsight.

Shruti Gohil, MD,MPH, Division of Infectious Diseases, University of California Irvine School of Medicine, Irvine, CA, and lead author of the study, discussed their findings and current infection control strategies with 

"Protective measures in the patient care setting did not change significantly after vaccination in healthcare—we maintained most of these regardless of vaccination, and have already begun reinforcing the need to maintain these precautions to all of our staff," Gohil said.

"After CDC and CDPH (California Department of Public Health) guidance came out to de-escalate prevention strategies in non-patient care areas, we did begin incorporating these guidelines," Gohil recounted."However, we are now reverting back to pre-vaccine levels of precaution in those areas as well."

Noting that their data were gathered before the delta variant, Gohil considered the possible different circumstances." Since vaccine efficacy is known to be lower for delta variant, we do expect more 'breakthrough' infections in vaccinated individuals," she said."But this does not equate to vaccine 'failure' since it is 96% effective against severe COVID that could result in hospitalization or death.

"What we are seeing here is very similar to influenza vaccine, which ranges in efficacy from 30 to 60% and yet is highly successful every year in curbing cases nationally and dramatically reducing risk of influenza-related hospitalizations and deaths," Gohil observed.

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Asymptomatic and symptomatic COVID-19 cases among health care personnel were reduced after vaccination despite surge in infected patients.

Vaccinations Protected Health Care Personnel During Surge of Patients with COVID-19

Exposure to antibiotics in early childhood had little effect on attaining body mass index (BMI) milestones and should not be a significant factor in pediatrician’ prescribing decisions, according to investigators who followed a large cohort receiving antibiotics within 48 months of birth.

"The small associations with BMI trajectory patterns after antibiotic exposure would likely have minimal clinical importance and should not affect the individual decision to prescribe antibiotics," Izzuddin Aris, PhD, Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, and lead author of the 

"Nevertheless, it remains unclear whether antibiotics causally influence obesity development in humans and whether particular antibiotic types are especially detrimental," Aris pointed out."From a public health perspective, excessive antibiotic exposure during early life remains a valid concern and antibiotic stewardship is an urgent priority, regardless of its potential role in obesity prevention."

The possibility that antibiotic use may be a modifiable risk factor for later childhood obesity has emerged from studies finding a small dose-response association with antibiotic exposure. It has been hypothesized that antibiotic effects on gut microflora result in altered energy metabolism and homeostasis, according to Aris and colleagues.

While previous studies have examined antibiotics and weight outcomes, it remains to be determined if, and how the age of exposure factors into an association, Aris remarked."Most of these studies have primarily focused on antibiotic exposures before 24 months of age, and few studies have investigated whether antibiotic after 24 months of age is associated with greater weight or alters longitudinal BMI trajectory patterns,"he said.

Aris and colleagues accessed the PCORnet, a collaborative data network from approximately 75 large health systems in the US, to identify a cohort of 183,444 children, 78.1% of whom had received antibiotics before 48 months of age, and whose records of height and weight allowed for estimable BMI peak and rebound in multiple age brackets, from 0-5 months, to 60-131 months.

"We chose to examine BMI growth milestones—BMI peak and rebound—as our outcomes because of its clinical significance and importance," Aris explained."An altered timing of these growth milestones—later age at BMI peak in infancy and earlier age at BMI rebound in early childhood—has been associated with excessive weight gain and cardiometabolic risk in later childhood."

The investigators report that exposure to any antibiotics at 0 to 5 months of age compared to no exposure was associated with later age (β coefficient, 0.05 months [95% CI, 0.02-0.08 months]) and higher BMI (β coefficient, 0.09 [95% CI, 0.07- 0.11]) at peak.Exposure to any antibiotics at 0 to 47 months of age compared to no exposure was associated with an earlier age (-0.60 months [95% CI, -0.81 to -0.39 months]) and higher BMI at rebound (β coefficient, 0.02 [95%CI, 0.01=0.03]).

Aris and colleagues found the strongest association for children with at least 4 episodes of antibiotic exposure.The association was stronger for those exposed to antibiotics at 24 to 35 months of age or 36 to 47 months of age than for those exposed at 0 to 5 months or 6 to 11 months of age.

"Effect estimates for associations with age at BMI rebound were larger for antibiotic exposure periods closer to the trajectory milestone," the investigators noted."The type of antibiotics—broad or narrow spectrum—did not substantively affect the pattern of the observed associations."

The apparently stronger association with antibiotic exposure closer to the trajectory milestone suggests to Aris that there may be "a short-term effect of antibiotic exposure on weight in infancy and childhood.

"This effect may not be sustained over the long term." he posited.

Exposure to antibiotics in childhood was found to have small effect on trajectory of body mass index milestones.

Antibiotics in Early Childhood Have Small Effect on BMI Milestones

A letter sent to primary care physicians (PCPs) in the highest 25th percentile of their peers in quantity or duration of antibiotic prescriptions resulted in modest reduction in duration and costs of drug treatment, but with less impact on the high number of prescriptions.

"Peer-comparison audit and feedback can be an effective tool to modify PCP behavior and improve patient outcomes," observed Kevin Schwartz, MD, Public Health Ontario, Toronto, Ontario Canada, and colleagues.

Schwartz and colleagues note that high and/or inappropriate use of antibiotics is associated with increases in patient- and ecological-level drug resistance, adverse drug effects, antibiotic drug costs; and can be driven, in part, by patients' expectations and their seeking health care for self-limited illnesses.

The investigators tested the letter as social normative feedback in a randomized controlled 

 to determine whether it could influence antibiotic prescribing patterns of PCPs who, they point out, are "crucial stakeholders and partners in antimicrobial stewardship efforts."

Schwartz and colleagues accessed centralized medication records of the Ontario province of Canada to rank family physicians and general practitioners by total number of antibiotic prescriptions, and the number of prescriptions in excess of 7 days duration provided during the period of March 1, 2017 to February 28, 2018.

The physicians ranked in the highest 25th percentile in total quantity of antibiotic prescriptions, or in prescriptions for amounts in excess of 7 days received letters indicating their ranking and describing guidelines for initiating antibiotic treatment, and/or of appropriate duration. The guidelines were drawn from recommendations and tools of the 

The letter was formulated in an iterative process for stakeholder engagement; with text developed in association with the Ontario Medical Association Section on General and Family Practice and cosigned by the Chair of the Section, and the Chief of Infection Prevention and Control at Public Health Ontario.

A total of 1484 PCPs received the letter on initiating antibiotic treatment, 1486 received the letter on optimal duration of treatment, and 496 serving as controls did not receive a letter.Prescribing was monitored for 12 months after the letter was sent.

Schwartz and colleagues reported that receipt of the initiation letter had no statistically significant effect compared to controls; but there was a statistically significant difference between the duration letter group and the initiation letter group on prolonged duration prescriptions.The initiation letter resulted in a 4.2% relative difference in overall ambulatory antibiotic prescribing.

The letter focusing on appropriate duration, however, resulted in a relative 8.1% fewer prolonged-duration prescriptions, with a corresponding 6.1% relative reduction in antibiotic drug costs.The investigators calculated that the duration letter resulted in an average of 24 fewer prolonged-duration and $771 in drug costs savings per PCP over 12 months.

The investigators characterized the intervention for high quantity prescribing as only "modestly effective at reducing antibiotic use".Further, they attributed the relative success of the duration letter to those performing most poorly at baseline, more likely to be in the later part of their career (≥25 years after medical graduation).

"In the present trial, we demonstrated that these same PCPs were considerably more likely to change their behavior in response to feedback," Schwartz and colleagues indicated.

In regard to the effectiveness of the single letter, the investigators acknowledge that "more marked reduction in appropriate antibiotic prescribing will require additional strategies."

Providing "social normative feedback" to physicians succeeded in lowering antibiotic treatment duration and cost, with less effect on prescription volume.

“Dear Dr" Letter Reduces Length and Cost of Antibiotic Treatment 

Fewer antibiotic prescriptions were prescribed for respiratory symptoms during the pandemic than in the comparable pre-pandemic period, in a 

 of ambulatory clinic patients of the University of Wisconsin Health system in southern Wisconsin.

Alexander Lepak, MD, Assistant Professor, Infections Disease Faculty, University of Wisconsin School of Medicine and Public Health, Madison, WI, and colleagues found that while antibiotic prescribing rates increased during the pre-pandemic winter respiratory viral season, they decreased in the short-term and remained low throughout the corresponding pandemic period.

"One way to interpret the study is to draw a conclusion about how much inappropriate antibiotic use was occurring for respiratory viruses in the pre-pandemic period.But I think there is another side to this story, and that this is a huge success story " Lepak told 

"We had massive COVID-19 surges, with unprecedented numbers of patients with respiratory complaints, especially in the Fall between October and December, yet antibiotics were not prescribed, for the most part, in patients with respiratory complaints during this period--keeping in mind they had indistinguishable symptoms from other respiratory viruses where antibiotics were previously prescribed."

Lepak and colleagues—with whom, Lepak emphasized, the study was a "huge collaborative effort"—compared the number of antibiotic prescriptions provided at the more than 80 ambulatory clinic sites of UW Health with 7 million annual ambulatory encounters, in the pre-pandemic period of July 2018 to February 2020 and April 2020 to February 2021 during the pandemic.The number of ambulatory encounters during those periods were similar: 637,000 and 662,000 per month, respectively.

The Winter seasonal viruses, including influenza, respiratory syncytial virus (RSV) and seasonal coronavirus, demonstrated seasonal variation during the prepandemic but not the pandemic period.The number of patients presenting with seasonal viruses decreased from approximately 4800 per month prepandemic to 12 per month in the pandemic period.Other respiratory virus detections also decreased, from 560 per month prepandemic to 228 per month during the pandemic.

The investigators reported that, adjusting for seasonality, monthly antibiotic prescription for respiratory tract infections (the indication for antibiotic prescriptions is required by UW Health Pharmacy) fell 79%, from 10.5 to 2.2 prescriptions per 1000 patient encounters.

"Antibiotic prescribing for respiratory complaints was best correlated with activity of seasonal Coronaviruses, Rhinoviruses, RSV, metapneumovirus, etc, and it was not as well correlated with influenza and wasn't correlated at all with COVID-19 activity," Lepak commented."The difference between these is that we have accessible and timely diagnostics for the latter two, but not necessarily the former group, at least for ambulatory care patients.

"Based on these findings, our hypothesis is that providing more comprehensive reepiratory viral testing that is accessible and timely to ambulatory providers and patients may be able to significantly curb antibiotic prescribing for respiratory viruses," Lepak said.

Although the investigators found other studies which have showed relatively quick declines in rates of viral infections or antimicrobial prescribing, they characterize theirs as "the first to combine respiratory virus activity and antibiotic prescriptions that were indexed to the number of encounters over a prolonged period that includes the typical respiratory virus season."

Increased respiratory viral testing for COVID-19 and Influenza could have contributed to improved antibiotic prescribing for respiratory symptoms.