COVID-19 occasionally associated with serious childbirth complications

Pregnant women with COVID-19 are more likely to experience complications such as heart attacks or blood clots, though the absolute increased risk is small, according to a JAMA Internal Medicine research letter today.

These findings highlight the need for risk mitigations, the authors write, adding that pregnant women should also be included in COVID-19 vaccine and treatment trials.

Using hospital codes within the US Premier Healthcare Database, the researchers looked at 406,446 hospitalizations for childbirth between Apr 1 and Nov 23, 2020. Of these, the 6,380 (1.6%) pregnant women who had COVID-19 were more likely to experience myocardial infarction (heart attack; adjusted odds ratio [aOR], 30.89), thrombotic (clot-producing) events (4.47), preeclampsia (1.21), and preterm birth (1.17). Absolute values ranged from less than 1% (myocardial infarction, 0.1% vs 0.004%) to almost 9% (preeclampsia, 8.8% vs 6.8%).

Mortality rate for COVID-infected pregnant women was 0.1%, which the researchers extrapolated to 141 deaths per 100,000 as opposed to the 5.0 deaths projected for non-infected women.

"Although the absolute risk differences were small, in-hospital death, [venous thromboembolism], and preeclampsia were considerably higher among women who gave birth with COVID-19 than in those without COVID-19," the author write.

COVID-19 infection was also associated with higher levels of care: 3.3% of pregnant women with COVID-19 were admitted to the intensive care unit (aOR, 6.47) and 1.3% needed mechanical ventilation (aOR, 23.70). Study data indicated that pregnant women with COVID were more likely to be younger (29.7% 24 years or under), black (17.6%) or Hispanic (42.6%), or experiencing diabetes (2.1%) or obesity (21.6%).
Jan 15 JAMA Intern Med study

Past COVID may give at least 83% protection against reinfection

While people who had COVID-19 infections may have protection against reinfection, viruses in their nasal and throat passages may still transmit the disease, according to a preprint paper outlining preliminary data on Public Health England's (PHE's) SARS-CoV-2 Immunity and Reinfection EvaluatioN (SIREN) study yesterday.

The study looked at 20,787 English healthcare workers from clinical and nonclinical roles from Jun 18 to Nov 24, 2020. Out of 6,614 workers who were placed in the COVID-19–positive cohort at time of recruitment, 42 developed possible and 2 developed probable reinfections, indicating an 83% protection rate (99% if the 42 possible reinfections were false).

The median interval between the participants' alleged infections was more than 160 days, or a little over 5 months.

Possible infections were defined as either having two positive polymerase chain reaction (PCR) tests more than 90 days apart or a new PCR-positive test at least 4 weeks after testing positive for COVID antibodies, according to a BMJ news story. Probable infections needed quantitative serologic or supportive viral genomic data in addition to this. Study participants had PCR and antibody tests every 2 to 4 weeks.

While a months-long immunity response is promising, the authors caution that more research needs to be done to explore vaccine effects, the development of SARS-CoV-2 variants, and transmission ability versus immunity. For instance, they write, those with immunity may still be able to carry the virus in their nasal and throat passages.

"This study has given us the clearest picture to date of the nature of antibody protection against COVID-19 but it is critical people do not misunderstand these early findings," Susan Hopkins, MB BCh, MSc, SIREN study leader, said in a PHE press release. "If you believe you already had the disease and are protected, you can be reassured it is highly unlikely you will develop severe infections but there is still a risk that you could acquire an infection and transmit to others."
Jan 14 PHE press release
Jan 14 BMJ news

Study shows high-dose, standard flu vaccines equally safe in older adults

A study yesterday in JAMA Network  Open compared the safety and short-term effects on quality of life in older adults who received either the trivalent adjuvanted inactivated influenza vaccine (aIIV3) or trivalent high-dose inactivated influenza vaccine (HD-IIV3), and found both are acceptable vaccine options for this patient population.

The randomized clinical trial included 757 adults 65 and older, with 378 receiving aIIV3 and 379 receiving HD-IIV3. The study included 420 women (55%) and 589 white participants (78%), with a median age of 72 for all patients.

According to the study authors, the proportion reporting moderate-to-severe injection-site pain, limiting or preventing activity, after aIIV3 (12 participants [3.2%]) (primary outcome) was noninferior compared with HD-IIV3 (22 participants [5.8%]) (difference −2.7%; 95% confidence interval, −5.8 to 0.4).

No vaccine-related serious adverse events occurred in either group, and the overall Health-Related Quality of Life (HRQOL) assessment scores were not clinically meaningful pre- and post-vaccination in either group.

"For older persons, any reaction that limits or prevents activities of daily living may have a substantial impact on quality of life," the authors concluded. "In our study, we measured quality of life change from baseline to 2 days postvaccination using HRQOL instruments validated for older adults. We found no significant differences in the change of prevaccination vs postvaccination HRQOL scores between the aIIV3 and HD-IIV3 groups."
Jan 14 JAMA Netw Open study

H5N6 and H9N2 avian flu cases reported in China

China reported one more human H5N6 avian flu case, in a 51-year-old man who works as a farmer near Chongqing, a city in the south-central part of the country, according to a recent avian flu update from the World Health Organization (WHO) Western Pacific regional office.

The man's symptoms began on Dec 18, and the investigation found that he had been exposed to domestic poultry. He was hospitalized with severe pneumonia on Dec 28 and is listed in critical condition. His illness lifts the number of H5N6 cases in China since 2014 to 27.

China reported two earlier cases in 2020; the last case was reported in December from Hunan province.

H5N6 outbreaks have been reported in poultry in China and other countries in Asia, but so far illnesses in humans—which are often severe or fatal—have been reported only in China.

Also, China reported another H9N2 avian flu case in a 1-year-old boy from Guangdong province who had been exposed to domestic poultry. His mild symptoms began on Dec 28, and he was hospitalized the following day. No other illnesses in family members were detected. The WHO said China has reported 42 H9N2 cases since December 2015.

Sporadic H9N2 infections have been reported in China and other countries where H9N2 is endemic in poultry. So far children are the most affected group, and the virus in humans has not been linked to sustained transmission.
Jan 8 WHO update

Three countries report more polio cases

Three countries—Pakistan, Sudan, and Yemen—reported more polio cases last week, all involving vaccine-derived virus, the Global Polio Eradication Initiative (GPEI) said in its latest weekly update.

Pakistan reported 1 circulating vaccine-derived poliovirus type 2 (cVDPV2) case in Sindh province, which is included in its total for 2020, which is now 122 for cVDPV2.

Sudan reported 4 cVDPV2 cases in four states: Kassala, Khartoum, Blue Nile, and Red Sea. The new cases raise the country's total for 2020 to 52. Also, Yemen reported 9 cases of circulating vaccine-derives poliovirus type 1 (cVDPV1) from Saadah, putting its 2020 total at 28.
Jan 14 GPEI update

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

Study finds antibiotics commonly dispensed without prescription in Africa

A systematic review and meta-analysis of 23 studies has found that dispensing of non-prescribed antibiotics outside of hospital settings is common in Sub-Saharan African countries, researchers reported yesterday in Antimicrobial Resistance and Infection Control.

To estimate the proportion of non-prescription antibiotic requests or consults that resulted in provision of antibiotics from community drug retail outlets (CDROs) in Sub-Saharan Africa, researchers from the University of Queensland, Australia, and the University of Gondar in Ethiopia conducted a literature search that yielded 23 studies, including 7 cross-sectional questionnaire-based surveys and 16 cross-sectional client-based studies. The studies were conducted in Ethiopia, Tanzania, Kenya, Sudan, Zimbabwe, Zambia, Ghana, Eritrea, Cameroon, and Uganda. The CDROs investigated included pharmacies, drug stores or shop, rural drug vendors, and accredited drug dispensing outlets.

A random-effect model meta-analysis of the data from these studies found that the overall pooled proportion of non-prescription antibiotic requests that resulted in the supply of antibiotics was 69%, ranging from 8% in Zimbabwe to 94% in Uganda. Upper respiratory tract infections and acute diarrhea were the most frequently presented case scenarios, and amoxicillin (26.5%) and co-trimoxazole (19.8%) were the most frequently dispensed antibiotics to treat those symptoms.

The study also found that non-prescription sale of antibiotics increased in Ethiopia, Kenya, Tanzania, and Zimbabwe even after those countries had adopted national action plans to combat antimicrobial resistance.

"Ease of access to and overuse can potentially accelerate the emergence of antibiotic resistance to few yet lifesaving antibiotics available in the region," the authors concluded. "Our review highlights the need for stringent enforcement of existing policies and/or enacting new regulatory frameworks that would regulate antibiotic supply, and continuous training and educational support for pharmacy personnel (e.g. pharmacists, pharmacy assistants) regarding judicious use of antibiotics and the importance of antimicrobial stewardship."
Jan 14 Antimicrob Resist Infect Control study

Study finds high rate of inpatient, outpatient antibiotic prescribing in Iran

In another study published yesterday in Antimicrobial Resistance and Infection Control, researchers reported high rates of inpatient and outpatient antibiotic prescribing in Iran.

The review and meta-analysis by Iranian and Dutch researchers looked at 54 studies published from 1995 through 2016, including 39 on outpatient prescribing and 15 on inpatient prescribing. The median rate of antibiotic prescribing in inpatient settings was 68.2%, with antibiotics prescribed for 39.5% of patients on all wards, 66% of patients on pediatric wards, and 75.3% of patients in intensive care units. The most commonly prescribed inpatient antibiotics were cephalosporins, penicillins, and carbapenems.

The median rate of antibiotic prescribing in outpatient settings was 45.3%. The mostly commonly prescribed outpatient antibiotics were penicillins, cephalosporins, macrolides, and aminoglycosides.

The study also found that traditional educational interventions to promote judicious antibiotic prescribing showed no significant effect on reducing the antibiotic prescribing rate.

The authors of the study say their findings highlight the need for Iranian policymakers to develop a national plan to improve antibiotic prescribing and consider the use of information technology–based interventions, such as clinical decision support systems, electronic health records, and electronic-based feedback on physician prescribing habits.
Jan 14 Antimicrob Resist Infect Control study

Study finds high antibiotic use in Indian hospitals

Originally published by CIDRAP News Jan 14

A point-prevalence study conducted in five hospitals in India shows high use of antibiotics in admitted patients, with a considerable proportion coming from a category of broad-spectrum drugs with a higher potential for promoting antibiotic resistance, Indian researchers reported in the Journal of Antimicrobial Chemotherapy.

The survey, conducted over 2 weeks in May 2019 at five tertiary care centers in India, aimed to collect data on antibiotic prescribing patterns and practices in the country's hospitals, which are in the nascent stages of developing antimicrobial stewardship programs. The researchers collected data on all admitted patients in wards and intensive care units over the study period to determine indications for antibiotic use and the percentage of patients on antibiotics, receiving more than one antibiotic, and on antibiotics from the Watch and Reserve categories of the World Health Organization's Essential Medicines List.

A total of 3,473 patients were included in the study. Of these patients, 1,747 (50.3%) were on antibiotics, with 46.9% being treated with two or more antibiotics. The most common indications for antibiotic use were community-acquired infections (40.6%), surgical prophylaxis (32.6%), and hospital-acquired infections (13.5%).

Drugs from the Watch category accounted for 80.6% of prescriptions, with third-generation cephalosporins being the most widely used. Carbapenems, considered Reserve antibiotics, accounted for 11.3% of antibiotic use.

The WHO's Access, Watch, and Reserve antibiotic classification framework was introduced in 2017 to provide an indirect indication of the appropriateness of antibiotic use at national and global levels. Watch antibiotics are broader-spectrum drugs that are not recommended for routine use because of their higher potential for promoting resistance, while Reserve antibiotics are considered last-resort antibiotics that should be used only for multidrug-resistant infections. The authors of the study say it is difficult to know whether the use of these antibiotics was appropriate or not.

"The findings of the survey were helpful in generating baseline data for identifying strategies for interventions directed at reducing antimicrobial use and for evaluating the impact of future interventions," the authors of the study wrote.
Jan 11 J Antimicrob Chemother abstract

High burden, increased resistance noted in invasive E coli infections

Originally published by CIDRAP News Jan 11

A new study led by researchers with Pfizer shows a substantial burden of extraintestinal invasive Escherichia coli infections (IEIs) in the United States, with increasing resistance to extended-spectrum cephalosporins.

In the study, published late last week in Clinical Infectious Diseases, researchers examined data from the Premier Healthcare Database, looking at all adult inpatient and hospital-based outpatient visits with continuous microbiology data submission from Jan 1, 2009, through Dec 31, 2016, for IEI events, which were defined as having a positive E coli culture from blood, urine, cerebrospinal fluid, or other normally sterile sites. The main outcome variables included count and prevalence of IEI events, risk of IEI occurrence, and the antibiotic resistance pattern of related IEI isolates.

The researchers analyzed more than 144.9 million hospital visits among more than 37.2 million patients during the study period and found that 71,909 IEI events occurred among 67,583 patients, corresponding to an IEI prevalence of 0.50 events per 1,000 visits and 1.82/1,000 patients. Among IEI patients identified, 58,168 (86%) were inpatients.

Prevalence among adults increased with age, ranging from 0.23/1,000 among patients 18 to 49 years to 1.3/1,000 among those 85 and over. Overall, 26.9/1,000 patients with IEI had a recurrent IEI in the 12 months following their initial infection. Urosepsis was the most common IEI, accounting for 66% of all infections, followed by bloodstream infections (22.1%).

Among all IEI cases with antibiotic susceptibility testing, 28.22% were resistant to fluoroquinolones, 9.18% were resistant to extended-spectrum cephalosporins, and 0.14% were resistant to carbapenems. Resistance to extended-spectrum cephalosporins increased from 5.46% to 12.97% during the study period.

"This high burden and acuity indicate that additional strategies for prevention are needed for IEI," the authors of the study wrote. "More research is needed to find effective ways to prevent these potentially deadly infections."
Jan 9 Clin Infect Dis study

Trial: Oral antibiotics alone not enough for uncomplicated appendicitis

Originally published by CIDRAP News Jan 11

The results of a randomized clinical trial involving adults with uncomplicated appendicitis show that treatment with oral antibiotics alone met the prespecified threshold for treatment success but failed to demonstrate noninferiority to intravenous (IV) antibiotics followed by oral antibiotics, researchers in Finland reported today in JAMA.

The open-label, noninferiority randomized trial was conducted from April 2017 to November 2018 in nine Finnish hospitals and included 599 patients with computed tomography–confirmed uncomplicated acute appendicitis. The purpose of the trial was to see whether oral antibiotics, which can be taken on an outpatient basis, could be an alternative to a combination of oral and IV antibiotics, which require hospital administration to ensure patient safety. An oral antibiotic regimen would shorten hospital stays and could enhance cost savings and patient satisfaction.

During the trial, a total of 295 patients received oral moxifloxacin for 7 days and 288 received IV ertapenem for 2 days followed by oral levofloxacin for 5 days. The primary end point was treatment success of greater than 65% for both groups. Treatment success was defined as hospital discharge without surgery and recurrent appendicitis during 1-year follow-up. The noninferiority margin was -6%.

The results showed that the treatment success rate was 70.2% among patients in the oral antibiotics group and 73.8% for patients treated with IV followed by oral antibiotics, for a difference of -3.6%. The confidence interval of the difference (-9.7%) exceeded the predefined noninferiority definition of a lower limit of -6%.

Despite the results, the authors of the study suggest the treatment success rate for oral antibiotics be considered during the COVID-19 pandemic in order to free up hospital resources at a time of bed capacity shortages and to reduce the risk of COVID-19 exposure for patients with uncomplicated appendicitis.

In an accompanying commentary, two experts with Nationwide Children's Hospital in Columbus, Ohio, wrote, "Additional studies related to nonoperative management of appendicitis no longer need to focus on the effectiveness of the treatment, but on further defining optimal treatment strategies. This includes antibiotic duration, mode of antibiotic delivery, the need for in-patient observation, and how to disseminate and promote implementation of nonoperative treatment choices across various practice types and patient demographics.
Jan 11 JAMA study 
Jan 11 JAMA commentary