Study shows strong 1-dose immune response with Pfizer vaccine

A single dose of the Pfizer-BioNTech COVID-19 vaccine was immunogenic in 92% of recipients, with no difference in immunogenic response between men and women but a decreasing response among older recipients, researchers from Israel's Bar-Ilan University reported yesterday in Eurosurveillance.

The research also showed that, among those with previous evidence of infection with SARS-CoV-2, the virus that causes COVID-19, the immune response to a single dose was significantly stronger.

In the study, 514 Israeli healthcare workers received the vaccine and had their antibody levels measured before vaccination and 21 days after the first dose. Of the recipients, 475 (92.4%) had detectable anti-SARS-CoV-2 spike immunoglobulin G (IgG) antibodies at 21 days. Among the responders, there was no statistically significant difference in antibody titers between men and women, but titers decreased with increasing age. The 39 healthcare workers who did not have a robust immune response to the first dose were older (median age 57 versus 47 in responders).

Compared with recipients who had not previously been infected, the 17 recipients with evidence of prior COVID-19 infection had post-vaccination IgG levels that were much higher (geometric mean concentration, 573 vs 61.5), regardless of whether IgG antibodies were detectable before being vaccinated.

"The boost-like response seen among previously infected individuals in our cohort suggests B-cell-mediated memory immunity is preserved regardless of IgG status," the authors wrote. "A single dose of vaccine in these individuals seems to boost the response although the optimal timing between infection and vaccination as well as the ensuing duration of protection remain to be determined."

In a Bar-Ilan University press release, the study's lead author suggested the findings could help countries make informed decisions on vaccine policy. "For instance, whether those previously infected should be vaccinated in priority and, if so, with how many doses," said Michael Edelstein, MBChB, MSc, an associate professor at Bar-Ilan University.

But Edelstein and his co-authors said the findings need be replicated on a larger scale in order to make such decisions.
Feb 11 Eurosurveill rapid communication
Feb 11 Bar-Ilan University press release

Early anticoagulant use tied to fewer deaths in VA patients with COVID-19

COVID-19 patients given preventive anticoagulants, or blood thinners, within 24 hours of hospitalization may have a greater chance of survival than those who don't receive them, suggests a large observational US Department of Veterans Affairs (VA) study published yesterday in BMJ.

A team led by researchers from the London School of Hygiene & Tropical Medicine mined the electronic health records of 4,297 VA patients hospitalized with COVID-19 from Mar 1 to Jul 31, 2020.

Of the 3,627 (84.4%) who received prophylactic anticoagulants (subcutaneous heparin or enoxaparin) on their first day in the hospital, 14.3% died within 30 days, compared with 18.7% of those who didn't receive the drugs (relative risk reduction [RR], 34%; absolute RR, 4.4%).

Patients who received anticoagulants had a 27% lower risk of death within 30 days than those who didn't receive them (hazard ratio [HR], 0.73). Similar associations were identified for inpatient death.

The anticoagulant benefit appeared to be greatest among patients not requiring intensive care unit admission within 24 hours of hospitalization. Anticoagulant use was not linked to an increased risk of serious bleeding requiring transfusion (HR, 0.87). Of the 4,297 patients, 93% were men; average age was 68 years.

Because coronavirus-related blood clots that develop in major arteries and veins can lead to death, the researchers aimed to see if anticoagulants, which have antiviral, and possibly anti-inflammatory, effects, could prevent coagulation. They noted that while previous studies had found evidence of the effectiveness of anticoagulants in coronavirus patients, they had small sample sizes or were conducted in relatively small healthcare systems.

"These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with COVID-19 on hospital admission," the authors wrote.

Clinical trials are being conducted to determine whether anticoagulants could be an effective treatment for coronavirus.
Feb 11 BMJ study

Hypoxemia, age, inflammation found in children with severe COVID-19

Hypoxemia (oxygen saturation below 95%), older age, and inflammation measured by C-reactive protein (CRP) levels were indications of severe COVID-19 infections in 397 French children hospitalized with the disease, according to a study published today in Pediatrics.

The study, which spanned patients hospitalized from Feb 15 to Jun 1, 2020, covered 35.8% of the country's pediatric COVID-19 cases.

Not including the children with multisystem inflammatory syndrome associated with COVID-19 (MIS-C) or those hospitalized for reasons other than COVID-19, 23 (7.5%) had severe infection, including 6 deaths. Severe cases were more common in children who were 10 or older (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1 to 10.3), hypoxemic (OR, 8.9; 95% CI, 2.6 to 29.7), or had a CRP of at least 80 milligrams per liter (OR, 6.6; 95% CI, 1.4 to 27.5).

MIS-C affected 29 (7.3%) of the cohort, of which 15 (51.7%) had severe cases. The researchers said their results support the idea that MIS-C occurs as a post-infectious event.

Overall, 20 of the children with severe cases needed invasive or noninvasive ventilator support, and 5 needed hemodynamic support.

While most hospital admissions were for children under 90 days old (36.5%), the researchers discovered that in this group, 58.6% had few symptoms, 40% were treated with antibiotics, and 68% were discharged with little care. In short, they write, most of these infants were most likely admitted because of an unknown fever and its risk of bacterial infection. Only four of the infants (2.8%) had severe infection.

The researchers included a seventh death in the study involving a child who had COVID antibodies but a negative reverse transcription polymerase chain reaction test, and these deaths made up all COVID pediatric deaths in the country during the study period. The average age was 9 years but ranged from 5 months to 17 years.

The authors conclude, "In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children <90 days old were at the lowest risk of severe disease evolution."
Feb 12 Pediatrics study

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Study touts revised antimicrobial prophylaxis protocol for ECMO patients

A revised antimicrobial prophylaxis protocol for patients on extracorporeal membrane oxygenation (ECMO) was associated with reduced broad-spectrum antimicrobial use in those patients, without increased risk of infection or poor outcomes, researchers from the Mayo Clinic reported today in Clinical Infectious Diseases.

In the quasi-experimental study, the researchers first compared prophylactic antimicrobial use and nosocomial infection rates in ECMO patients in the 3 years prior to the introduction of the protocol in July 2014 and the 3 years after. Under the protocol, antimicrobials with a broader spectrum of activity were selected for prophylaxis (prevention) in patients with prosthetic valves or cardiovascular devices. Antibiotic prophylaxis is common in ECMO patients because of their high risk of infection.

After initial analysis of the data and feedback colleagues, the researchers revised the protocol to recommend narrower-spectrum agents and included active infectious disease (ID) clinician involvement with real-time audit and feedback. They then reevaluated the data, comparing the period before the protocol with the period following implementation of the original protocol and the period following implementation of the revised protocol. The study population included 338 patients who received ECMO from July 2011 through November 2019.

The mean rate of antimicrobial use (expressed as antimicrobial days per ECMO days) did not change significantly from the pre-protocol period (1.98 days; 95% confidence interval [CI], 1.82 to 2.15) through the original protocol period (2.06 days; 95% CI, 1.90 to 2.23), but then declined significantly in the third period (1.09 days; 95% CI, 0.94 to 1.25), with the decline applying primarily to broad-spectrum antimicrobials. The observed reduction in broad-spectrum antimicrobials did not result in significant increases in nosocomial infection rates, length of intensive care unit stay, ventilation time, or mortality.

The authors say the revised protocol was more restrictive and consistent with its approach to antimicrobial use in ECMO patients, and that audit and feedback from ID specialists provided an enforcement mechanism that the original protocol lacked.

"A multidisciplinary team-based approach to antimicrobial stewardship can significantly reduce antimicrobial prophylaxis and overuse in ECMO patients without increased risk of nosocomial infection," they wrote. "These data can be used to assist other institutions in developing protocols for appropriate antimicrobial use in this population, balancing the threat of antimicrobial resistance and side effects with prevention of nosocomial infections."
Feb 12 Clin Infect Dis abstract

Antibiotic prescribing in telehealth can be appropriate with guidance, study finds

Originally published by CIDRAP News Feb 10

Telemedicine visits in Brazil performed under rigorous adherence to antibiotic stewardship guidelines were associated with appropriate antibiotic prescribing for patients with low-risk conditions, Brazilian and Australian researchers reported yesterday in the International Journal of Infectious Diseases.

While some studies have suggested that antibiotic prescribing rates for people who consult telemedicine services may be higher than those who have face-to-face visits with providers, most of these studies have not specified the protocols and guidelines accessible to providers or how telemedicine providers should be trained and monitored for antibiotic stewardship.

In this study, researchers assessed antibiotic prescribing at a hospital in Sao Paulo, where all telemedicine providers were required to be trained on international antibiotic stewardship protocols based on the best current evidence, and senior supervisors monitored prescription rates.

The study included all patients 18 and older who sought telemedicine consultations for acute but non-urgent symptoms through the hospital from January 2019 through February 2020. Diseases for which an antibiotic might be required were classified into five diagnostic groups: upper respiratory tract infection (URI), acute pharyngotonsillitis (PT), acute sinusitis (AS), urinary tract infection (UTI), and acute diarrhea (AD).

Of the 2,328 patients included, 2,085 (89.6%) received telemedicine consultations alone, and 243 (10.4%) were referred for face-to-face consultation. Among the telemedicine patients, 472 (22.6%) received an antibiotic. The antibiotic prescribing rates per diagnostic group were 2.5% for URI, 35% for PT, 51.8% for AS, 1.6% for UTI, and 1.6% for AD. In most cases, these prescriptions were in line with international stewardship protocols, and the prescribing rates were low compared with other telemedicine programs, the authors concluded.

"This study shows that using technology and proper antibiotic stewardship may mitigate the apprehension that video visits may lead to a high antibiotic prescription rate," they wrote.
Feb 9 Int J Infect Dis abstract

Macrolide resistance found in 40% of US Strep pneumoniae isolates

Originally published by CIDRAP News Feb 10

A surveillance study published last week in Open Forum Infectious Diseases found macrolide resistance in 40% of Streptococcus pneumoniae isolates from adult ambulatory and inpatient settings in US hospitals.

Using microbiology laboratory data from the BD (Becton, Dickinson and Company) Insights Research Database, researchers evaluated S pneumoniae blood or respiratory cultures with antibiotic susceptibility test results collected at 329 US hospitals from October 2018 through September 2019. The pathogen is the most common bacterial cause of community-acquired pneumonia (CAP), an illness that results in more than 1 million emergency department visits and an estimated 750,000 to 1 million hospitalizations annually.

Isolates with resistance to azithromycin, clarithromycin, or erythromycin were considered macrolide-resistant. The researchers used US Census geographic regions and ZIP code tabulation areas to determine the regional distribution of resistant isolates.

The overall rate of macrolide resistance among 3,626 S pneumoniae isolates analyzed was 39.5%, with a significantly higher resistance rate found in respiratory isolates (47.3%) than in blood isolates (29.6%). Isolates from ambulatory settings had a higher rate of resistance than isolates from inpatients (45.3% vs 37.8%).

Evaluation of regional resistance found the highest rate of macrolide resistance in the West North Central region (54.2%), followed by the South Atlantic (48.0%). Although geographic variations were observed, most regions had overall macrolide resistance rates higher than 25%, and more than 25% of respiratory isolates in all regions were macrolide-resistant.

The authors say the results, along with other recent US or North American studies showing high macrolide resistance in S pneumoniae, may explain recent findings of high failure rates (21%) with macrolide monotherapy in patients with CAP. They say ongoing surveillance efforts are needed to track resistance trends in S pneumoniae and suggest that clinicians in most parts of the country consider alternatives to macrolide monotherapy as empiric therapy for suspected CAP.
Feb 4 Open Forum Infect Dis abstract

Resistance to 3 or more antibiotics in 13% of serious urinary infections

Originally published by CIDRAP News Feb 9

One in eight US patients hospitalized with a complicated urinary tract infection (cUTI) have a pathogen with resistance to three or more routinely used antibiotic classes, researchers reported yesterday in BMC Infectious Diseases.

To assess the prevalence of overlapping resistance to antibiotics commonly used to treat cUTIs and its impact on patient outcomes, the researchers conducted a retrospective study of patients hospitalized with a culture-positive carbapenem-susceptible cUTI using data from approximately 180 US institutions that submitted microbiology data from 2013 through 2018.

Triple resistance (TR) was defined as resistance to three or more common antibiotics: third-generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin.

Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on patient mortality, 30-day hospital readmission, hospital length-of-stay (LOS), and costs.

Among 23,331 patients with a cUTI, 13% (3,040) had a TR pathogen. Compared with patients with non-TR pathogens, those with TR pathogens were more likely to be male (57.6% vs 47.7%), black (17.9% vs 13.6%), and located in the South (46.3% vs 41.5%).

They also had a higher chronic disease burden (median Charlson comorbidity score, 3 vs 2) and a higher acute disease burden (mechanical ventilation, 7.0% vs 5.0%; intensive care unit [ICU] admission, 22.3% vs 18.6%). Patients with a TR pathogen were more likely to receive IET than those without (19.6% vs 5.4%).   

Although the adjusted outcomes showed that TR was not associated with a rise in hospital mortality or 30-day readmission rate, it added 0.38 days to hospital LOS (95% CI, 0.18 to 0.49) and $754 to hospital costs (95% CI, $406 to $1,103). In patients with a cUTI that was not catheter-associated, however, TR was associated with increased risk of mortality (odds ratio, 2.44; 95% CI, 1.30 to 4.56).

"In summary, we have demonstrated that resistance to combinations of regularly used antimicrobials is prevalent and on the rise in the most common cUTI organisms in the US hospitals," the authors wrote. "Though increasing resistance alone does not impact hospital mortality, it does expose patients to an elevated risk of worsened outcomes through increasing the likelihood of inappropriate empiric therapy."
Feb 8 BMC Infect Dis study

PAHO issues epidemiologic alert on Candida auris

Originally published by CIDRAP News Feb 8

The Pan American Health Organization (PAHO) late last week issued an alert on outbreaks of Candida auris in the Americas, noting an increase in cases of the multidrug-resistant yeast during the COVID-19 pandemic.

While several countries in the region have reported isolated cases or small outbreaks of C auris since 2012, four countries with no previous history of the pathogen (Brazil, Guatemala, Mexico, and Peru) reported cases during the last 6 months of 2020, with a hospital in Mexico reporting an outbreak involving 10 patients in an intensive care unit. In addition, Panama and Colombia reported 124 and 340 C auris cases, respectively, in 2020. Most cases have been reported in patients with COVID-19.

First identified in Japan in 2009, C auris spreads easily in healthcare settings, can cause serious invasive infections in immunocompromised patients, and has shown resistance to three major antifungal drug classes. Recent case reports, including an investigation of a C auris outbreak at a Florida hospital in July 2020, have linked COVID-related breakdowns in infection prevention and control to the spread of the pathogen in hospitals.

To prevent hospital outbreaks, the PAHO alert recommends that health services build capacity for early detection of patients with suspected C auris infections or colonization, isolate cases in single rooms when recommended, screen all patients on the same hospital ward, clean and disinfect the patient area and surfaces with disinfectant effective against C auris on a daily basis, and reinforce hand hygiene among healthcare workers.

PAHO also recommends that hospitals notify health authorities of any positive C auris isolates identified by validated methods.
Feb 6 PAHO epidemiologic alert