Stewardship / Resistance Scan for Oct 28, 2019

News brief

TB Alliance picks Indian firm to manufacture, commercialize pretomanid

Nonprofit drug developer TB Alliance announced today that it will partner with an Indian company to manufacture and commercialize pretomanid for treating extensively drug-resistant tuberculosis (XDR-TB).

TB Alliance is granting Macleods Pharmaceuticals Limited of Mumbai a non-exclusive license to manufacture pretomanid, which was approved by the US Food and Drug Administration (FDA) in August as part of a three-drug, 6-month regimen for treatment of patients who have XDR-TB. The all-oral regimen, known as BPaL (bedaquiline, pretomanid, and linezolid), is significantly shorter than current treatment regimens for XDR-TB, which last 18 to 24 months.

"TB Alliance is committed to ensuring an affordable, sustainable and competitive market for all our new TB products," Mel Spigelman, MD, president and CEO of TB Alliance, said in a press release. "We are proud to partner with Macleods, which has a strong record of delivering high-quality, affordable tuberculosis medicines."

Pending approval from other regulatory agencies, Macleods will make pretomanid available in about 140 countries and territories.
Oct 28 TB Alliance press release

Germany reports outbreak of carbapenem-resistant Klebsiella

At least 17 patients at three German hospitals and a rehabilitation clinic have been infected with carbapenemase-producing (with resistance genes NDM-1 and OXA-48) and colistin-resistant Klebsiella pneumoniae ST307, according to a risk assessment today from the European Centre for Disease Prevention and Control (ECDC).

The outbreak is taking place in Mecklenburg-West Pomerania in northeast Germany. As of Oct 21, 6 of the 17 patients presented with clinical symptoms, while 11 were identified as carriers, the ECDC said.

"This is the first reported outbreak in Germany of K. pneumoniae that produce both NDM-1 and OXA-48 while also involving the emerging clone ST307," the ECDC said. The outbreak strain is closely related to the same carbapenemases detected earlier this year in Finland from a patient previously hospitalized in Russia, but there is no epidemiologic link between the Finnish case and the outbreak in Germany.

The ECDC said the risk to individuals outside healthcare settings is low, but the strain shows markers of increased virulence. Officials warned that not all European countries have effective screening systems in place for carbapenemase-producing Enterobacteriaceae, adding that German hospitals have put in place enhanced control measures.
Oct 28 ECDC risk assessment

FDA approves Baxdela for community-acquired pneumonia

The FDA has approved the supplemental New Drug Application (sNDA) for Baxdela (delafloxicin) for the treatment of community-acquired bacterial pneumonia (CABP), drug maker Melinta Therapeutics, Inc., announced last week, but its launch for that indication will be delayed.

FDA approval was based on the results of a phase 3 clinical trial that found that intravenous (IV)-to-oral Baxdela was noninferior to IV-to-oral moxifloxacin in early clinical response at 96 hours after initiation of therapy (88.9% vs 89%) and success at test of cure visit (90.5% vs 89.7%). Data also showed that Baxdela successfully eradicated key pathogens at rates comparable to moxifloxacin, and it was well-tolerated by study participants.

Baxdela was initially approved by the FDA in 2017 for use in patients with acute bacterial skin and skin-structure infections.

But Melinta, of Morristown, New Jersey, also said the commercial launch of Baxdela for CABP will be delayed because of the company's financial troubles.

"As previously disclosed, we are closely managing our liquidity position and continue to evaluate our potential strategic and other alternatives," interim CEO Jennifer Sanfilippo, JD, said in a press release. "As such, while we believe that Baxdela will play a significant role in the treatment of this potentially life-threatening illness, we are delaying the commercial launch of CABP until we have greater insight into our ability to secure additional sources of liquidity."
Oct 24 Melinta press release

News Scan for Oct 28, 2019

News brief

MERS infects Saudi boy, representing 10th case this month

Saudi Arabia reported a MERS-CoV infection in a child, which is relatively rare, according to an Oct 26 report from the country's Ministry of Health (MOH).

The patient is a 10-year-old boy from the city of Unayzah in Qassim region, which is located in the central part of Saudi Arabia. The boy's exposure to the virus is listed is primary, meaning he probably didn't contract the illness from another patient. His recent contact with camels is listed as unknown.

So far, Saudi Arabia has reported 10 MERS-CoV (Middle East respiratory syndrome coronavirus infections in October, up from 4 in September.

Since the first human cases were detected in 2012, the World Health Organization as of the end of September has received reports of 2,468 cases, at least 851 of them fatal. The vast majority of the illnesses have been reported in Saudi Arabia.
Oct 26 Saudi MOH statement

Alabama reports fatal EEE case, lifting US total to 36

Alabama health officials recently reported a human Eastern equine encephalitis (EEE), its first since 2014, according to an Oct 25 statement from the Alabama Department of Public Health (ADPH).

The patient from Baldwin County, located in the state's southwestern corner, got sick in September and died from the infection. Earlier this year, EEE was reported in a mosquito and sentinel chicken sample from neighboring Mobile County and from a horse in Houston County, which is in the southeastern corner.

Sherri Davidson, PhD, MPH, interim state epidemiologist, urged people to continue taking precautions against being bitten by mosquitoes, especially as the weather becomes more pleasant and conducive to outdoor activities.

The latest development from Alabama brings the number of states reporting human cases this year to nine and the number of confirmed cases to 36. In an update last week, the US Centers for Disease Control and Prevention (CDC) said it has received reports of 35 cases from 8 states.

Nationally, EEE cases are up sharply, given that only about 7 cases are reported to the CDC each year. Massachusetts, Michigan, Connecticut, and Rhode Island are among the hardest-hit states. EEE infections are rare, but when they occur are most commonly reported in areas near hardwood swamps in Atlantic and Gulf Coast states and in the Great Lakes region.
Oct 25 ADPH press release
Oct 22 CDC EEE background

Philippines, Pakistan report more polio cases

Both the Philippines and Pakistan reported new polio cases in recent days, with Pakistan's infection raising that country's year-to-date total to 77 cases.

In the Philippines, officials confirmed a third case of vaccine-derived poliovirus type 2 in the country's first outbreak in two decades, according to CNN Philippines. Philippines Health Secretary Francisco Duque III said the third confirmed case involves a 4-year-old girl from Maguindanao province who had not received the oral polio vaccine.

Government officials said they would begin a polio vaccination campaign on Nov 4 through 8 targeting more than 4,250 children ages 0 to 59 months.

Meanwhile, Pakistani newspaper Dawn said a 9-month-old boy from Khyber Pakhtunkhwa was diagnosed as having polio, and has become the 77th case recorded in Pakistan this year, compared to a total of 12 cases in 2018 and 8 cases in 2017.

The boy's parents did not vaccinate their child, the newspaper said, because they believe the polio vaccine is either haram (prohibited by Islamic law) or it makes their children impotent.

Pakistan and Afghanistan are the only remaining countries in the world with endemic wild poliovirus circulation. According to a new study in Clinical Infectious Diseases, three major geographic reservoirs in Pakistan—Karachi, Peshawar, and Quetta block—carry more than three quarters of the burden of poliovirus infection.
Oct 28 CNN Philippines story
Oct 27 Dawn article
Oct 26 Clin Infect Dis study

Study suggests prenatal Zika infection tied to possible language delay

A new study suggests prenatal Zika infection is linked to lower receptive language scores in the first year of life even in the absence of microcephaly or congenital Zika syndrome. The study appeared late last week in JAMA Network Open.

Researchers from Harvard University and the University of Puerto Rico School of Medicine looked at 65 Puerto Rican infants enrolled in existing Zika studies to assess cognitive developments from ages 3 to 6 months and 9 to 12 months. The infants were tested in fine and gross motor skills, visual reception, receptive language, and expressive language. Enrollment was based on maternal Zika status.

The authors of the study found no significant cognitive differences between the 29 babies from Zika-positive mothers and the 36 from Zika-negative mothers, except in receptive language skills. Infants whose mothers tested negative for Zika prenatally had a mean score of 49.42 (standard deviation [SD], 10.98) in receptive language, and those whose mothers tested positive prenatally had a mean score of 43.90 (SD, 9.98).

"Receptive language skills were also associated with the degree of exposure to Hurricane Maria, with those who spent more time without water after the hurricane having lower receptive language scores," the authors said.
Oct 25 JAMA Netw Open study