The American College of Physicians (ACP) has released updated guidance on COVID-19 treatments for outpatients infected with the currently predominant Omicron variant that favors a couple of antiviral drugs. The American College of Physicians (ACP) has released updated

The practice points were based on a review by Danube University Krems researchers on the risks and benefits of 22 COVID-19 treatments. The team searched the Epistemonikos COVID-19 L·OVE platform, the iSearch COVID-19 portfolio, and the World Health Organization COVID-19 Research Database from November 26, 2021, to March 2, 2023.

The results were published yesterday in the Annals of Internal Medicine.

Paxlovid, molnupiravir 'probably' improve outcomes

The researchers identified two randomized, controlled trials and six retrospective studies involving patients with mild to moderate COVID-19. The antiviral combination nirmatrelvir-ritonavir (Paxlovid) was tied to lower rates of COVID-19 hospitalization (eg, 0.7% vs 1.2%; moderate certainty of evidence [COE]) and all-cause death (eg, <0.1% vs 0.2%; moderate COE).

Molnupiravir, an antiviral, was linked to a higher recovery rate (31.8% vs 22.6%; moderate COE) and faster recovery (9 vs 15 median days; moderate COE) but didn't affect all-cause death (0.02% vs 0.04%; moderate COE) or serious adverse events (0.4% vs 0.3%; moderate COE).

The anti-parasite drug ivermectin didn't lessen time to recovery (moderate COE) or adverse events compared with placebo (low COE). Sotrovimab, a monoclonal antibody, showed no difference in all-cause death compared with no treatment (low COE). No eligible studies for other treatments of interest were identified.

The decision to initiate treatment for COVID-19 in the outpatient setting should be personalized and based on clinical judgment using an informed decision-making approach with the patient.

"Nirmatrelvir–ritonavir and molnupiravir probably improve outcomes for outpatients with mild to moderate COVID-19," the researchers wrote. Paxlovid is given to outpatients who have had symptoms for no more than 5 days and are at high risk for severe illness.

The ACP said it will update the guidance as new evidence emerges. "The decision to initiate treatment for COVID-19 in the outpatient setting should be personalized and based on clinical judgment using an informed decision-making approach with the patient on potential treatment benefits, harms, patient characteristics (such as risk factors, comorbid conditions, and disease severity), patient preferences, and social determinants of health," the researchers wrote.

The United Nations Refugee Agency and the World Health Organization (WHO) today sounded the alarm about a deepening health crisis in war-torn Sudan, where about 1,200 children younger than 5 from nine refugee camps have died over the past 4 months due to a suspected measles outbreak and malnutrition.

In a statement, Filippo Grandi, the UN's high commissioner for refugees, said the world has the means and money to prevent all of the deaths, which are the result of a devastating conflict and a lack of global attention. "We can prevent more deaths, but need money for the response, access to those in need, and above all, an end to the fighting."

Shortages of staff, equipment, and supplies at Sudan's healthcare facilities are exacerbated by attacks on the facilities, patients, and the transport of medical supplies, the groups said, adding that the country is also battling cholera, dengue, and malaria outbreaks. Tedros Adhanom Ghebreyesus, PhD, the WHO's director-general, said, "We call on donors to be generous and on the warring parties to protect health workers and access to health for all those who need it."

Neighboring countries receiving fleeing Sudanese refugees are seeing the impacts firsthand. South Sudan is reporting increasing numbers of children with measles and malnutrition arriving from Sudan, especially from White Nile state. In Ethiopia's Amhara region, a cholera outbreak is emerging at sites hosting more than 18,000 people who have fled the conflict in Sudan, with 8 deaths and 435 suspected cases amid low supplies of cholera vaccine. And health providers in Chad are reporting high levels of malnutrition in children among those who have fled Sudan.

The two UN groups continue to provide urgent assistance in Sudan and neighboring countries, including food and measles vaccine distribution to children in camps in the countries Blue and White Nile states.

The Pan American Health Organization (PAHO) recently posted an epidemiologic alert about a rise in dengue cases in Central America and the Caribbean regions, urging countries to review their response plans and step up surveillance ahead of the Southern Hemisphere's summer season.

So far this year, about 3.4 million dengue cases have been reported in the Americas, exceeding the record 3.1 million cases recorded in 2019. Brazil by far has been the hardest-hit country in 2023, followed by Peru and Bolivia. Brazil has also reported the highest number of severe cases, followed by Colombia, Peru, Bolivia, and Mexico. So far this year, 1,612 dengue deaths have been reported in the Americas, putting the case-fatality rate at 0.05%.

In Central and North America, Nicaragua has been the hardest-hit country this year, with cases 83% higher than the same period in 2022 and 1.87 times higher than the 5-year average. Mexico's cases this year are triple that of 2022 and are double the 5-year average. Cases are also above 2022 and 5-year averages in Costa Rica and Guatemala.

In the Caribbean, the Dominican Republic, Martinique, and Guadeloupe have been the top hot spots, and in the United States, Puerto Rico has reported 374 locally acquired cases, with cases also reported in Florida and Texas.

PAHO said the seasonal rise in activity and the onset of the rainy season in the second half of 2023 has burdened some healthcare systems in Central America and the Caribbean, a signal that countries entering their summer season prepared their health systems to cope with an expected rise in cases.

Florida reports 4 more local dengue cases

In related developments, Florida in its latest weekly surveillance update reported 4 more local dengue cases, raising the year's total to 23. Most cases this year were reported in Miami-Dade County, with a few in Broward, Hardee, and Polk counties. Two cases involved non-Florida residents.

Of 22 subtyped samples, 17 infections were from dengue serotype 3, with 4 from serotype 2, 1 from serotype 1, and 1 from an unknown serotype.

The Global Fund to Fight AIDS, Tuberculosis, and Malaria today announced a new collaboration with Danaher Corporation to drop the price of Cephid's diagnostic test cartridges for tuberculosis (TB) by 20%, which will allow 5 million more tests to be provided and expand access to high-quality testing in low- and middle-income countries.

The test cartridge price will drop from $9.98 to $7.97, and Danaher—Cephid's parent company—will make no profit on the tests. The deal between the Global Fund and Cephid also includes improved service and maintenance arrangements.

Peter Sands, the Global Fund's executive director, said in a statement, "Reducing the price of these sophisticated TB tests by 20% will give a significant boost to our collective efforts to scale up testing and save lives." The group added that Cephid Xpert cartridges are especially important for diagnosing drug-resistant TB.

Meanwhile, Lucica Ditiu, MD, executive director of the Stop TB Partnership, said the drop in price is significant and gives countries two rapid molecular tests below $8, making them more affordable for countries with small budgets for battling TB.

Today's announcement is part of ongoing efforts by the Global Fund, the Stop TB Partnership, the US Agency for International Developments, and other partners to work with Cephid and Danaher to improve access to affordable testing. The efforts are part of a global goal to end TB by 2030.

New York-based biotechnology company ContraFect announced yesterday that it has submitted an investigational new drug (IND) application to the US Food and Drug Administration for a compound that targets lung infections caused by multidrug-resistant gram-negative bacteria.

The IND was filed to support the launch of first-in-human clinical trials testing ContraFect's investigational intravenous antibiotic, CF-370, in patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). CF-370 is an engineered lysin therapeutic candidate that has demonstrated potent activity against Pseudomonas aeruginosa—one of the gram-negative pathogens commonly implicated in HABP/VABP—in in vitro experiments and animal infection models.

Novel mechanism of action

In July 2020, ContraFect was awarded a grant by the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) for funding of up $18.9 million to support development of CF-370, which works by bypassing the tough outer membrane of P aeruginosa.

"We are thrilled to advance this program into clinical studies," ContraFect chief medical officer W. Garrett Nichols, MD, said in a company press release. "CF-370's unique activity profile and novel mechanism of action provide the basis for its potential as a new treatment paradigm for treating these patients, especially those with resistant Gram-negative infections that further increase the probability of poor outcomes, including death."

HABP/VABP are the most common type of healthcare-associated infection in acute care hospitals and are a significant issue for patients in intensive care units, who are frequently on ventilators. Rising antibiotic resistance has made these infections increasingly challenging to treat.

ContraFect says it hopes to begin a phase 1 clinical trial later this year.