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

New Web site details CDC investments in fight against antibiotic resistance

Originally published by CIDRAP News Jan 12

The Centers for Disease Control and Prevention (CDC) has released a new online tool that will enable users to find out how the agency is financially supporting efforts to combat antibiotic resistance across the country.

The CDC AR Investment Map is an interactive site where you can click on individual states to find out how much money the CDC is providing in fiscal year 2016 to state health departments to help tackle antibiotic resistance. The site also includes a detailed breakdown of the funding for each state by activity, including investments in public health laboratories to help identify antibiotic-resistant threats more quickly, in healthcare-associated infection control programs to prevent the spread of drug-resistant bugs, and in efforts to improve antibiotic use.

Overall, Congress appropriated $160 million to the CDC in 2016 to fight antibiotic resistance. The agency says the investments detailed on the new Web site will work toward meeting national goals to prevent drug-resistant infections as outlined in the National Action Plan for Combating Antibiotic-Resistant Bacteria.
CDC Antibiotic Resistance Investment Map

Study describes drug-resistant Candida auris biofilms

Originally published by CIDRAP News Jan 12

A study today in Emerging Infectious Diseases reports that Candida auris, a drug-resistant yeast that's been associated globally with life-threatening invasive diseases, has the capacity to form antifungal-resistant biofilms.

In the study, researchers grew biofilms from strains of C auris and compared them with biofilms grown from C albicans and C glabrata, two other types of yeast that can also cause invasive infections. Biofilms are complex communities of bacteria that form on any surface exposed to bacteria and water and can tolerate higher doses of antibiotics than their planktonic counterparts. Biofilm formation, the authors write, "is a key driver of C albicans pathogenicity and is associated with patient death."

The researchers found that C auris formed biofilms that were significantly reduced compared with C albicans but much greater than the biofilms formed by C glabrata. And when they tested the C auris biofilms and planktonic cells against a selection of antifungal agents, they found that the biofilms could resist some of the agents that were active against planktonic cells. The researchers were particularly interested to find that the antifungal caspofungin, which is normally highly effective against Candida biofilms, was inactive against C auris biofilms.

"These features contribute not only to C auris virulence but also to its survival in hospital environments, increasing its ability to cause outbreaks," the authors write.

The disinfectant chlorhexidine, however, was effective, exhibiting the greatest activity against C auris biofilms and planktonic cells. As a result, the authors conclude that while it is unlikely that the spread of C auris can be controlled by antifungal stewardship approaches alone, chlorhexidine "can be advocated for topical control of C auris at standard concentrations for skin and wound cleaning and disinfection."

C auris was first identified in the ear of a Japanese patient in 2009 and has caused hospital outbreaks across Asia and South America. In November, the CDC said 13 cases have been identified in the United States.
Jan 12 Emerg Infect Dis dispatch

Colistin-resistance gene found in Salmonella isolates from Chinese pigs

Originally published by CIDRAP News Jan 10

A gene that confers resistance to the last-resort antibiotic colistin has been detected in nearly 15% percent of Salmonella isolates from pigs in southern and central China, researchers report yesterday in Emerging Infectious Diseases.

The researchers obtained 142 Salmonella isolates from pigs at five slaughterhouses and screened them for the MCR-1 gene using polymerase chain reaction (PCR) and genetic sequencing methods; 21 (14.8%) of the isolates tested positive for MCR-1, a plasmid-mediated gene that was first identified by Chinese researchers in 2015 among Escherichia coli isolates from Chinese pigs, pork products, and hospital patients.

Susceptibility testing showed that all 21 isolates were resistant to colistin and that more than 80% were resistant to ampicillin, streptomycin, florfenicol, tetracycline, sulfamethoxazole/trimethoprim, and gentamicin. In addition, 76.2% showed reduced susceptibility to ciprofloxacin.

The authors report that most of the isolates were clonally related to serovar Typhimurium sequence type 43, which is common in Salmonella isolates from humans in China and other countries and has been linked to food-producing animals.

In three of the isolates, the MCR-1 gene was found on derivatives of IncHI2-like plasmids, which the authors note have been frequently associated with the global spread of MCR-1 genes. Plasmids, which are mobile pieces of DNA, enable the horizontal transfer of resistance genes between different types of bacteria and as a result can fuel faster spread of antibiotic resistance.

Since the MCR-1 gene was first identified in 2015, it has been found in more than 30 other countries. Although mainly found in E coli, it has also been found in Salmonella and several other Enterobacteriaceae.

"Spread of similar IncHI2-like plasmids and Salmonella Typhimurium ST34 clones carrying mcr-1 in different countries highlights the need for internationally coordinated intervention strategies to limit its further dissemination," the authors write.
Jan 9 Emerg Infect Dis dispatch

Analysis indicates tedizolid is an alternative option for MRSA skin infections

Originally published by CIDRAP News Jan 9

A meta-analysis of 15 clinical trials has found that tedizolid could be an alternative option for the treatment of serious skins infections caused by methicillin-resistant Staphylococcus aureus (MRSA), researchers recently reported in BMC Infectious Diseases.

For the review, researchers combed 10 databases to find studies that estimated the relative effectiveness of tedizolid, an oxazolidinone-class antibiotic, and established monotherapy comparators (including vancomycin, daptomycin, linezolid, and ceftaroline) for treating acute bacterial and skin structure infections caused by MRSA. Vancomycin has historically been the standard treatment for MRSA, but concerns about slow bactericidal activity and the emergence of resistance have called its efficacy into question.

Outcomes of interest included clinical response at end of therapy (EOT), post-therapy evaluation (PTE), and treatment of discontinuations resulting from adverse events (AEs).

Among the 15 trials that met the inclusion criteria, fixed-effect models showed that tedizolid had higher odds for clinical response at EOT (OR, 1.7) and at PTE (OR, 1.6) than vancomycin, but there was no evidence of a difference between tedizolid and the other comparator drugs in odds of clinical response for EOT or PTE. In addition, there was no evidence of a difference between any of the treatments for discontinuation because of AEs.

"These findings suggest that tedizolid provides an alternative option for the management of serious skin infections caused by suspected or documented MRSA," the authors write. They note, however, that the study is subject to the limitations inherent in all network meta-analyses (including quality of included studies, publication bias, and limited data), and the results should be interpreted accordingly. 
Jan 7 BMC Infect Dis study

Study: Low doses of aminoglycosides for MDR-TB can reduce hearing loss

Originally published by CIDRAP News Jan 9

A study today from Dutch researchers indicates that lower doses of aminoglycosides for the treatment of multidrug-resistant tuberculosis (MDR-TB) can reduce one of the drugs' more significant side effects while still remaining effective.

In a study published in Antimicrobial Agents and Chemotherapy, investigators from the University of Gronningen retrospectively evaluated 80 patients treated for MDR-TB from 2000 to 2012. The patients received doses of 6.5 mg/kg/day of amikacin and kanamycin, the aminoglycosides that form the cornerstone of MDR-TB treatment. While World Health Organization guidelines recommend 15 mg/kg/day, hearing loss and nephrotoxicity have been observed in 8% of 37% of patients receiving those drugs for any period.

The purpose of the study was to evaluate a strategy that used lower doses of aminoglycosides based on the susceptibility of the infection to the drugs and the concentration of the drugs in patients' blood.

Overall, the investigators found that lower doses of the drugs resulted in less hearing loss for the patients, with only 9 of the 70 patients (12.9%) who were available for audiometry tests showing hearing loss at high decibels. And of the 52 patients with available clinical data, 35 (67.3%) had successful outcomes, with none of the patients having a documented treatment failure or relapse.

These results, the authors write, suggest that "the efficacy at this lower dosage is maintained with limited toxicity" and provide enough evidence for a prospective randomized trial.

"After more than 30 years of medical practice prescribing aminoglycosides in a dose of 15 mg/kg, we believe that a formal study is warranted between standard of care, and an individualized approach based on drug susceptibility and drug concentrations," they write.
Jan 9 Antimicrob Agents Chemother abstract