Stewardship / Resistance Scan for May 01, 2019

News brief

US Candida auris case count tops 600

Confirmed and probable Candida auris cases in the United States through Mar 31 rose to 643, an increase of 56 from the end of February, the Centers for Disease Control and Prevention (CDC) said in an update yesterday.

Illnesses caused by the multidrug-resistant fungus have been reported in 12 states, though 95% are in New York (323), Illinois (160), and New Jersey (128). The other states reporting cases are California (2), Connecticut (1), Florida (13), Indiana (1), Maryland (3), Massachusetts (7), Oklahoma (2), Texas (2), and Virginia (1).

Of the 643 cases, 613 are confirmed and 30 are listed as probable. Screening for C auris has found an additional 1,123 patients who are colonized. The number of colonized patients has grown by 67 since the CDC's last update. The screening is part of the CDC's efforts to control the spread of the fungus, which is known to persist on surfaces in healthcare facilities and spread among patients.

Since its first identification in 2009 in Japan, C auris has triggered outbreaks in healthcare facilities in more than 20 countries and has shown resistance to three major antifungal drug classes. C auris can cause serious invasive infections in patients who have compromised immune systems, and the CDC has estimated that 30% to 60% of patients with infections have died.
Apr 30 CDC C auris case count

 

FDA turns down new antibiotic candidate over manufacturing concerns

Citing concerns about manufacturing standards, the US Food and Drug Administration (FDA) has rejected Nabriva Therapeutics' New Drug Application (NDA) for Contepo (fosfomycin for injection) for complicated urinary tract infections (cUTIs), including pyelonephritis.

Dublin-based Nabriva announced yesterday that the FDA has asked the company to address issues related to facility inspections and manufacturing deficiencies at one of its contract manufacturers before approving the NDA, but did not request any new clinical data or raise safety concerns about the drug. Nabriva said it plans to request a "Type A" meeting to discuss the FDA's findings.

"We need to meet with the FDA to get a better understanding of the issues identified during the facility inspection, what concerns remain based on the responses submitted during the expedited 4-month review process, and whether or not the manufacturer's corrective actions sufficiently addressed them," Nabriva CEO Ted Schroeder said today during a company conference call.

Contepo is an investigational, intravenous formulation of fosfomycin that has been used outside the United States for cUTIs and other infections for 45 years. Currently, only oral fosmfomycin is FDA-approved for treating cUTIs. Nabriva believes Contepo could be a first-in-class treatment because it has activity against gram-positive and gram-negative pathogens, including multidrug-resistant (MDR) strains, and it uses a new dosing approach that optimizes the compound's pharmacokinetics and pharmacodynamics.

The FDA previously granted Contepo Qualified Infectious Disease Product and Fast Track designations for cUTIs, complicated intra-abdominal infections, hospital-acquired and ventilator-associated bacterial pneumonia, and acute bacterial skin and skin-structure infections.
Apr 30 Nabriva press release

 

Study suggests shorter empiric antibiotic course for neonatal sepsis

A study today in the Pediatric Infectious Disease Journal suggests that empiric antibiotics with gram-negative coverage for infants who have suspected early-onset sepsis (EOS) can be safely stopped after 24 hours.

The retrospective analysis of blood samples collected from the neonatal intensive care unit at McMaster Children's Hospital in Ontario over a 10-year period included 7,480 blood cultures (from 9,245 neonates) that were sent to the microbiology laboratory for evaluation of sepsis.

The investigators used BacT/Alert 3D, an automated microbial detection system that can identify positive blood samples faster than traditional blood culture methods. The aim was to analyze the time taken to detect positive blood cultures and determine whether empiric antibiotics could be discontinued by 24 or 36 hours to rule out sepsis. Generally, clinicians wait 48 hours before deciding to discontinue antibiotics, but concerns about inappropriate antibiotic use have prompted re-evaluation of this practice.

Of the 7,480 blood cultures performed, 885 grew microorganisms, and 845 culture reports from 627 neonates were analyzed. Definite or opportunistic pathogens caused 815 infections (96%), and the rest were contaminants. EOS accounted for 54 of the positive cultures, and late-onset sepsis (LOS) for 791. Gram-negative organisms grew faster than gram-positive organisms, with 99% of gram-negatives having detectable growth by 24 hours, compared with 67.2% of gram-positives. Cultures from EOS were positive significantly earlier than LOS. After adjusting for covariates, gram-negative status was an independent predictor of early detection of a positive blood culture (hazard ratio, 3.5; 95% confidence interval [CI], 2.7 to 4.5).

"This suggests that empiric antibiotics with Gram-negative coverage can be safely stopped if the 24-hour BacT/Alert is reported negative, provided there are no clinical or laboratory parameters suggesting sepsis," the authors of the study write. "Empirical Gram-positive coverage can be stopped between 48 and 72 hours, particularly if there is no setting for an opportunistic infection, such as prematurity, immunodeficiency or indwelling catheters."
May 1 Pediatr Infect Dis J study

 

Longer surgical prophylaxis linked to higher risk of adverse events

A national cohort study of patients in the Veterans Administration (VA) healthcare system has found that increasing the duration of surgical antibiotic prophylaxis was not associated with additional reductions in surgical-site infection (SSI), but it was associated with increases in adverse events in a dose-dependent fashion. The findings appeared in JAMA Surgery.

In the study, a team led by researchers with the VA Boston Healthcare System analyzed data on 79,058 patients who underwent cardiac, total joint replacement, colorectal, and vascular procedures in the VA healthcare system from October 2008 through September 2013. The outcomes of interest were 30-day SSI, 7-day incidence of acute kidney injury (AKI), and 90-day incidence of Clostridioides difficile infection. The exposure variables of interest were duration and type of surgical prophylaxis.

After adjusting for SSI risk factors, the researchers found that antibiotic courses lasting more than 24 hours did not lead to reductions in SSI among any of the types of surgery evaluated. But adjusted odds of AKI increased with each additional day of prophylaxis, rising by 3.2% in cardiac procedures after 24 to less than 48 hours (adjusted odds ratio [aOR], 1.03; 95% CI, 0.95 to 1.12), by 22.3% after 48 to less than 72 hours (aOR, 1.22; 95% CI, 1.08 to 1.39), and by 82.0% after 72 hours or more (aOR, 1.82; 95% CI, 1.54 to 2.16). A similar increase in AKI risk was observed for non-cardiac procedures.

Odds of C difficile infection for all procedures increased nonsignificantly by 7.8% after 24 to less than 48 hours of antimicrobial prophylaxis (aOR, 1.08; 95% CI, 0.89 to 1.31) and significantly increased by 142.6% after 48 to less than 72 hours (aOR, 2.43; 95% CI, 1.80 to 3.27) and by 265.1% after 72 hours or more (aOR, 3.65; 95% CI, 2.40 to 5.55).

The analysis also found that use of vancomycin was a significant risk factor for AKI in cardiac procedures (aOR, 1.17; 95% CI, 1.10 to 1.25) and noncardiac procedures (aOR, 1.21; 95% CI, 1.13 to 1.30). 

The authors conclude, "These data should be used to inform policy surrounding surgical prophylaxis and may have broader implications for antimicrobial stewardship programs aiming to reduce harms associated with unnecessary antimicrobial exposures. Every day—and every dose—matters."
Apr 24 JAMA Surg study

News Scan for May 01, 2019

News brief

Philippines measles outbreak linked to Dengvaxia troubles

A growing measles outbreak in the Philippines is being fueled by vaccine hesitancy that originated in the Dengvaxia vaccine controversy, which has embroiled that nation for the last 3 years.

According to a report today from UNICEF and the World Health Organization (WHO), there have now been 31,056 measles cases, including 415 deaths (case-fatality rate, 1.34%) reported in the Philippines since Jan 1, which is 368% more cases than the number recorded during the same period last year.

The outbreak is connected to low vaccine uptake, a problem that has worsened after Dengvaxia, Sanofi Pasteur's dengue vaccine, was widely administered to school-age children in the Philippines despite evidence the vaccine could lead to severe dengue cases in some recipients.  

Last year, the Philippines recorded 20,827 measles cases and 199 deaths. The outbreak in the Philippines has also been connected to US measles cases.

"Outbreak and supplementary immunization activities in 2018 were ineffective in addressing the outbreak as the immunization activity was met with increased vaccine hesitancy due to the Dengue vaccine controversy," the report said.
May 1 UNICEF-WHO report

 

French study notes emergence of enterovirus strain tied to neuropathy

French investigators have detailed the recent emergence of a recombinant enterovirus A71 (EV-A71) strain associated with neurologic disease in recent years in France that has the potential to be associated with a long-term risk for severe disease among children, according to a study yesterday in Emerging Infectious Diseases.

National surveillance data from 2016 revealed 77 cases of infection with EV-A71 subgenogroup C1v2015 lineage viruses, one of seven genogroups of the virus. In comparison, France saw 136 total EV-A71 infections from 2010 through 2015.

The C1v2015 cases were widespread throughout the country and associated with various conditions, including meningitis, cerebellitis, encephalitis, and myelitis, as well as hand, foot, and mouth disease (HFMD). "One fatal case resulted from HFMD and cardiorespiratory failure," the authors report.

Whole-genome sequencing revealed that the C1v2015 substrain "appears to be a mosaic comprising 4 modules defined by distinct patterns of similarity possibly arising through recombination." The researchers note that the close genetic relatedness between the French C1v2015 and those reported in 2015 through 2017 in Germany, Japan, and the United States indicated rapid widespread transmission. They surmise that person-to-person spread of this lineage began during 2009 to 2011 and was sustained in 2013 and 2014, just 1 to 2 years before C1v2015 was first reported.

The authors conclude, "Given the propensity of enteroviruses to recombine their genomes and spread rapidly across distant countries and that C1v2015 circulation continued throughout 2017 and 2018 in France, we need to determine if this virus is associated with a long-term recurrent risk for severe disease in the pediatric population through sharing of data from global surveillance."
Apr 30 Emerg Infect Dis study

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