New fluoroquinolone for bacterial skin infections wins FDA approval

A new fluoroquinolone antibiotic, delafloxacin (Baxdela), for acute bacterial skin and skin structure infections (ABSSSI) in adults gained approval yesterday from the US Food and Drug Administration (FDA), according to Melinta Therapeutics, the manufacturer.

Delafloxacin is active against both gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus, the company said in a press release. It is available in oral and intravenous (IV) formulations.

"The approximately 3 million patients hospitalized each year in the US with ABSSSI often present treatment challenges owing to their underlying medical conditions, making optimal antibiotic selection difficult," said Melinta CEO Eugene Sun, MD. "Baxdela provides a treatment option for adult patients with ABSSSI based on its coverage spectrum, IV and oral dosing flexibility, efficacy and safety profile."

The company reported that two phase 3 studies in patients with ABSSSI showed that IV and oral delafloxacin monotherapy was statistically non-inferior to the combination of vancomycin and aztreonam at the FDA primary endpoint of early clinical response at 48 to 72 hours. The drug was well tolerated, with a 0.9% discontinuation rate due to adverse events.

In addition, delafloxacin has not shown any potential for QT-segment prolongation or phototoxicity in definitive clinical studies, Melinta said, adding, "There have been no signs of adverse effects on liver function, kidney function, or glucose regulation in controlled clinical studies." The 450-mg tablet is biologically equivalent to the 300-mg IV dose and can be given without regard to food intake, the statement said. There are no anticipated drug interactions with delafloxacin other than with chelating agents, such as antacids.

Gram-negative ABSSSIs for which delafloxacin is indicated include those caused by Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa, according to Melinta.

The FDA gave the drug priority review because of its designation as a Qualified Infectious Disease Product (QIDP) under the Generating Antibiotic Incentives Now (GAIN) Act of 2012, the company noted.
Jun 19 Melinta press release
FDA information on delafloxacin

CDC findings suggest MDR-TB burden in US children is underestimated

National surveillance suggests that the rate of multidrug-resistant tuberculosis (MDR-TB) in US children over a recent two-decade period was less than 2%, but the limited use of bacteriologic testing in TB cases means the true rate is probably higher, according to federal, state, and local researchers.

The findings by authors from the Centers for Disease Control and Prevention (CDC), California, Minnesota, and New York City were published yesterday in Clinical Infectious Diseases.

They analyzed data on newly diagnosed TB cases in children under age 14 that were reported to the National TB Surveillance System (NTSS) from 1993 through 2014. MDR TB was defined as culture-confirmed TB disease with resistance to at least isoniazid and rifampicin. To assess potential underestimation of pediatric MDR-TB, they surveyed high-TB–burden states for clinically diagnosed cases that were treated for MDR-TB.

Of 20,789 pediatric TB cases, 5,162 (24.8%) involved bacteriologically confirmed disease, the team found. Among 4,862 (94.2%) cases with drug-susceptibility testing, 82 (1.7%) involved MDR-TB. Fifty-one of the 82 (62%) patients were female, with a median age of 5 years. A third (28; 34%) were Hispanic, and two-thirds (55; 67%) were born in the United States.

Most cases (66; 80.5%) showed resistance to at least one other first-line drug, and one-third (24 of 73 tested) were resistant to one or more second-line drugs, the report says. Of 77 patients who started treatment before 2013, 66 (86%) completed treatment and 4 (5%) died.

The researchers calculated that among the four high-burden states and jurisdictions surveyed, pediatric MDR-TB cases were underestimated by 42% to 55% when using only culture-confirmed case definitions.

"Only one-quarter of pediatric TB cases had culture-confirmed TB, likely resulting in underestimation of true pediatric MDR TB burden in the US using strictly bacteriologic criteria," the team concluded. "Better estimates of pediatric MDR TB burden in the US are needed and should include clinical diagnoses based on epidemiologic criteria."
Jun 19 Clin Infect Dis abstract

Study: Testing for flu—but not other viruses—affects prescribing

For patients hospitalized with respiratory illness, rapid testing for influenza clearly influences antimicrobial prescribing decisions, but test results for other viruses have less impact, a study conducted over three winters in a large Montreal hospital suggests.

In the prospective study, described yesterday in the Journal of Infectious Diseases, 800 patients admitted to the hospital with respiratory illness were tested for 12 viruses, including flu. The authors hypothesized that positive flu tests would lead to appropriate antiviral therapy and decreased use of antibiotics, and that positivity for other viruses would lead to stopping oseltamivir and antibiotics.

Most of the patients were started on antibiotic treatment before they were tested for viruses. Flu was identified in 53% of the patients, and other viruses were found in 10%. In patients not already on oseltamivir treatment, clinicians were nine times more likely to start oseltamivir if they tested positive for flu than if they tested negative, and flu positivity was associated with shorter hospital stays.

Patients who were started on antibiotics before the viral testing and then had a positive flu test were roughly 1.4 times more likely to have their antibiotics discontinued than were those who tested negative, but the association was not statistically significant after adjusting for potential confounders such as age and comorbidity, the authors said.

Antibiotic management was most significantly correlated with radiologic suspicion of pneumonia—even though radiologic findings don't reliably distinguish between bacterial and viral pneumonia—and was less correlated with the viral test results, the authors found. "Positivity for other viruses was not correlated with significantly different outcomes."

"Merely providing access to rapid multiplex testing may not be sufficient to reduce antibiotics, even during winter when influenza and other viral pathogens are frequent," the report concludes. "The ability to interpret positive results in the context of clinical illness, and the legitimate concerns of bacterial co-infections need to be addressed."
Jun 19 J Infect Dis abstract

Survey gauges physician support for penalizing inappropriate prescribing

A Web-based survey of members of the American College of Physicians indicates that clinicians are more likely to support financial penalties for routine antibiotic prescribing when presented with information about patient harms.

In the survey, published today in the Annals of Internal Medicine, physicians were presented with a clinical vignette to measure how likely they were to recommend antibiotics for uncomplicated upper respiratory infection. They were also asked about their attitudes regarding cost control in patient care.

The physicians were randomly assigned to one of four versions of the principal question, which evaluated how likely they were to support a policy that financially penalized physicians and organizations for routinely prescribing antibiotics for such infections. The first version described the harm to patients from routine antibiotic prescribing (increased costs, iatrogenic infections), the second version described the harms to society (increased antibiotic resistance, diversion of limited healthcare resources to less productive uses), the third described increased costs to institutions (hospitals and insurers), and the fourth version described no harms.

The first three versions included the statement "According to research and expert opinion, mild to moderate upper respiratory symptoms lasting less than 7 days are frequently due to viruses and therefore resolve on their own."

Of 694 eligible respondents, 47% completed the survey. The mean age of the respondents was 48 years, 55% were male, and 90% were practicing physicians. Overall, 31% supported financial penalties, but that number rose to 41% among those assigned the patient harm version, compared with 36% assigned the institutional harm version, 23% of those assigned the societal harm version, and 25% of those given the control version. Support for financial penalties was also higher among physicians who agreed that clinicians should play an active role in cost control (31%) than among those who disagreed (14%).

The authors of the survey say the preliminary results suggest that emphasizing the harms and costs to patients could increase the acceptability of financial penalties for routine antibiotic prescribing.
Jun 20 Ann Intern Med survey

CDC: US Candida auris cases rise to 86

In its latest update on infections involving Candida auris, an emerging multidrug-resistant fungus, the US Centers for Disease Control and Prevention (CDC) said it has received reports of 9 more illnesses, raising the total to 86.

One of the new cases is in Florida, raising the number of affected states to eight. That case involved a C auris sample that was collected in April. According to the CDC update, posted Jun 16, New Jersey and New York both have new cases with positive samples collected in May.

In a May 18 Morbidity and Mortality Weekly report on 77 cases, the CDC said many of the patients had epidemiologic connections and that many in the two hardest-hit states—New York and New Jersey—had overlapping stays at connected long-term care facilities and hospitals. New York now has 60 cases and New Jersey 17, according to the update. No other state has more than 4 cases.

C auris was first identified in 2009 in Japan and has emerged as a global health threat because of its growing resistance to all three major classes of antifungals used to treat Candidainfections. The CDC estimates the mortality rate of C auris infections at approximately 60%.
Jun 16 CDC Candida auris page
May 18 CIDRAP News scan

Meta-analysis finds self-medication a 'massive' problem in Middle East

Self-medication, including with antibiotics, is a major problem in the Middle East, a new review of 72 studies has found.

As noted in the Pharmacology Research & Perspectives meta-analysis, investigators identified research published from 1990 through 2015. Misused medicines included codeine-containing products, topical analgesics and corticosteroids, antimalarial drugs, and antibiotics. Self-medication was widespread, and pharmacists, friends, and parents were the main sources of drugs.

One study determined that in Syria 87% of 200 pharmacies agreed to sell antibiotics without a prescription. The figure increased to 97% when those seeking the drugs insisted. Another study found that pharmacies in Iran sold 57% of prescription items without a prescription. In Saudi Arabia, only one pharmacist refused to dispense medications without a prescription.

"There has been relatively little systematic research on this topic, partly due to the perception that self-medication misuse is not as problematic as other types of drug abuse," said lead author Malak Khalifeh, in a news release from Wiley, the journal's publisher. "This review has found a massive problem."
Jun 18 Pharmacol Res Perspect review
Jun 19 Wiley news release

OpGen's gene-profile antibiotic resistance testing advances

OpGen, Inc., of Gaithersburg, Md., yesterday announced it has entered into an agreement to use Thermo Fisher Scientific's technology to support the commercialization of its rapid molecular products and informatics system to help combat multidrug-resistant infections.

OpGen will combine Thermo Fisher's real-time polymerase chain reaction (PCR) testing with its genomic analysis and bioinformatics technology to help healthcare providers rapidly identify antibiotic susceptibility in bacteria by using resistance gene profiles.

Under the agreement, OpGen will commercialize the Acuitas Rapid Test for Pathogen ID and resistance genes on Thermo Fisher's new mid-throughput real-time PCR system. The effort will be supported by local labs that will interpret results using customized analysis software and OpGen's database to match genomic analysis data with antibiotic susceptibility information to identify microbial infections in individual patients.
Jun 19 OpGen press release