ASP Scan (Weekly) for Apr 21, 2017

Marker for pneumonia antibiotics
MCR-1 cases in Italy
Novel antibiotic target
Penicillin-resistant pneumonia
ID stewardship consults
Steroid for sore throat
MRSA contamination
Chlorhexidine bathing
Candida in Peru
Azithromycin and abnormal heartbeat
Mutations in resistant bacteria

Study shows promise for procalcitonin to guide pneumonia treatment

Spanish investigators reported in PLoS One yesterday that procalcitonin (PCT) level is an effective marker in point-of-care testing for selecting narrow-spectrum antibiotics in outpatients who have pneumonia.

PCT is a protein and precursor to the hormone calcitonin that is produced by immune cells after a bacterial infection. Increasing evidence has shown its usefulness as a biomarker for diagnosing sepsis and bacterial infections.

In the new study, the researchers used PCT levels as measured with rapid point-of-care testing to guide treatment for community acquired pneumonia. Based on test results, 216 adults (those with lower PCT levels) were prescribed azithromycin and 37 were prescribed levofloxacin. They compared the results in these patients to a control group of 493 adults who were treated using historical standard-of-care methods.

The researchers recorded clinical cure rates of 95.8% in the azithromycin group, 94.6% in the levofloxacin group, and 94.4% in the control group. No 30-day mortality or recurrences were noted, and all groups had low 3-year rates of recurrence and mortality and low rates of adverse events.

The authors conclude, "A PCT-guided strategy with a rapid point-of-care testing safely allowed selecting empirical narrow-spectrum antibiotics in outpatients with CAP."
Apr 20 PLoS One study


Italian scientists report 3 MCR-1 bloodstream infections

Italian scientists yesterday in Eurosurveillance detailed three cases of MCR-1–positive Escherichia coli bloodstream infections, a worrisome indication of resistance to colistin, an antibiotic of last resort.

The cases involved a woman in her 70s with cancer who was hospitalized for a respiratory infection in July 2016, a woman in her mid-60s with a diagnosis of non-Hodgkin's lymphoma treated in August 2016 who died within 5 days, and a woman in her early 80s with fever, diarrhea, and abdominal pain who was hospitalized in January. All had previously received chemotherapy for cancer. None had ever been treated with colistin, had recent contact with farm animals, or reported recent travel.

Whole-genome sequencing detected the MCR-1 gene in three E coli strains of different sequence types isolated from blood samples from the three women.

MCR-1, which confers resistance to colistin, was first identified in China in November 2015 in E coli samples from pigs, pork products, and humans. It has since been detected in more than 30 countries and is especially worrisome because it resides on small gene segments called plasmids that can transfer among various pathogens.
Apr 20 Eurosurveill report


New drug takes novel approach to inhibiting bacterial growth

Originally published by CIDRAP News Apr 20

A study today in the Canadian Journal of Physiology and Pharmacology describes a novel antibiotic agent that targets a different pathway than traditional antibiotics to inhibit bacterial growth.

In the first part of the study, a team of Canadian researchers explain how sodium ion circulation enzymes, or pumps, serve as a direct source of energy in many bacterial pathogens. They identified one enzyme in particular, the NQR pump, as critical for the growth and proliferation of Chlamydia trachomatis, a species of gram-negative bacteria that causes chlamydia infections. Identifying a novel target for antibiotic activity is considered critical to the development of new antibiotics.

In the second part of the study, the researchers showed that PEG-2 and PEG-2S, compounds extracted from the antibiotic korormicin (which is too toxic to be an effective treatment), inhibit the growth and proliferation of C trachomatis bacteria by suppressing the function of the NQR pump. And because the drugs only target bacteria harboring NQR enzymes, they don't affect healthy cells and non-pathogenic gastrointestinal bacteria.

The researchers say that since NQR enzymes are present in other bacterial pathogens, such as Pseudomonas aeruginosa and Neisseria gonorrhea, their findings have implications beyond the inhibition of growth in C trachomatis, and that PEG-2 and PEG-2S may potentially be used to suppress bacterial growth in a number of different diseases.

"The results from our collaboration are tremendously exciting," lead author and University of Manitoba professor Pavel Dibrov, MSc, PhD, says in a press release from journal publisher Canadian Science Publishing. "We are currently designing PEG-2S variations and hope to tailor PEG-based antimicrobials to each specific NQR-containing pathogenic bacterium." 

PEG-2S has received a provisional patent, according to the press release
Apr 20 Can J Physiol Pharmacol study 
Apr 20 Canadian Science Publishing press release


US study shows no increase in penicillin-resistant pneumonia

Originally published by CIDRAP News Apr 20

Researchers from Harvard University and the US Centers for Disease Control and Prevention (CDC) reported no significant change in the prevalence of penicillin resistance among nonvaccine pneumococcal strains after the introduction of the 13-strain pneumococcal conjugate vaccine (PCV13) in the United States, but with wide regional variations.

As noted in their report in Emerging Infectious Diseases, the investigators used data from the Active Bacterial Core surveillance system, a population- and lab-based collaborative system between the CDC and state health departments and academic institutions in 10 states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York, Oregon, and Tennessee. They compared serotypes isolated in 2009 and 2012. PCV13 was implemented in 2010.

They found that PCV13 introduction was not associated with a significant change in the prevalence of penicillin resistance in nonvaccine serotypes "because of the variable success of highly resistant serotypes." They added that differences in regional serotype distribution and serotype-specific resistance contributed to geographic heterogeneity of penicillin resistance.

Georgia, New Mexico, and Minnesota had the highest level of penicillin resistance in 2012, while Oregon had the lowest, followed by California and Tennessee.
Apr 18 Emerg Infect Dis report


Study finds ID consultation helps patients with S aureus bacteremia

Originally published by CIDRAP News Apr 19

Adding infectious disease consultation to antimicrobial stewardship review in the management of patients with Staphylococcus aureus bacteremia (SAB) can ensure adherence to recommended treatment and improve clinical outcomes, according to a study yesterday in the American Journal of Infection Control.

In the retrospective cohort study, investigators at University of Chicago Medicine, an academic medical center, evaluated adult patients with SAB who were admitted for treatment from December 2012 through October 2014. The investigators were looking to see whether the inclusion of ID consultation (IDC) in the management of SAB, which has been shown to improve cure rates and reduce rates of recurrence in previous studies, would have an impact in a setting where SAB patients are already evaluated by an antimicrobial stewardship program (ASP).

The primary end point of the study was the incidence of complete adherence to a composite of SAB treatment guidelines from the Infectious Diseases Society of America (IDSA). The composite included at least one echocardiogram, daily blood cultures until at least 72 hours of negative cultures, removal of prosthetic devices, initiation of appropriate antibiotics with activity against methicillin-resistant S aureus (MRSA) if necessary, and de-escalation to beta-lactams if MRSA was not present. Secondary outcomes included length of stay, recurrence of SAB within 8 weeks, and all-cause mortality.

Of the 154 patients included in the study, 115 received IDC, and 39 did not. The investigators found that adherence to the composite of IDSA guidelines was 78% in the patients who received IDC, compared with 46% in the patients who received no consultation, with significantly more IDC patients receiving echocardiograms (91% vs. 67%) and daily blood cultures (92% vs. 64%) than non-IDC patients. In addition, mortality was much lower in the IDC group than in the non-IDC patients (5% vs. 23%).

Although there were no differences in initiation of appropriate antimicrobial therapy or de-escalation, the authors of the study say that finding is likely a result of the hospital's ASP, which already provides recommendations on antimicrobial therapy.

"These results provide supporting evidence for requiring automatic consult with ID specialist physicians for patients with SAB," the authors write.
Apr 18 Am J Infect Control study


Oral steroid without antibiotic might aid in sore throat relief

Originally published by CIDRAP News Apr 19

In a JAMA study yesterday that has potential antibiotic-sparing implications, a single dose of the oral steroid dexamethasone provided symptom relief for sore throat in 48 hours but not within 24 hours, and the difference between the drug and placebo was modest.

The clinical trial involved 565 UK adults who visited acute care clinics with sore throats that did not require immediate antibiotics. Of the total, 293 patients received 10 milligrams of dexamethasone and 283 received a placebo, with the patients and physicians not knowing which they received. Sore throat imposes a substantial burden on primary care and is a frequent source of inappropriate antibiotic prescribing.

Twenty-four hours after taking the pills, 65 patients in the treatment group (22.6%) and 49 in the placebo group (17.7%) reported complete resolution of symptoms, a statistically non-significant difference. At 48 hours, however, the percentages rose to 35.4% and 27.1%, respectively, which reflected a statistically significant difference.

The rate of complete symptom relief was about 31% higher in the dexamethasone group after 48 hours, and the difference was seen whether the patients were offered a delayed antibiotic prescription or not.
Apr 18 JAMA study


Study details MRSA glove, gown contamination in VA nursing homes

Originally published by CIDRAP News Apr 19

A study involving seven Veterans Administration (VA) nursing homes in four states and Washington, DC, found a 20% rate of MRSA glove contamination and an 11% rate of gown contamination in healthcare workers, with certain high-risk activities increasing the odds of gown contamination.

VA researchers in Maryland, New York, Massachusetts, Texas, and Washington, DC, enrolled 200 residents in the study, which was published yesterday in the American Journal of Infection Control. Of those residents, 94 (46%) were found to be colonized with MRSA.

The team then determined that 20% of healthcare workers contacting the colonized patients had glove contamination, compared with 11% for gown contamination, with transmission varying from 7% to 37% for gloves and from 0% to 19% for gowns. The authors identified changing wound dressing, providing hygiene such as brushing teeth, and bathing as high-risk activities for gown transmission.

The authors conclude, "Transmission to gloves varies by type of care, but all care had a risk of contamination, demonstrating the importance of hand hygiene after all care. . . . Optimizing gown and glove use by targeting high-risk care activities could improve resident-centered care."
Apr 18 Am J Infect Control study


Daily ICU chlorhexidine baths tied to low rates of MDR microbes

Originally published by CIDRAP News Apr 19

Daily chlorhexidine bathing in the intensive care unit (ICU) was associated with low levels of multidrug-resistant (MDR) organisms, according to a third study yesterday in the American Journal of Infection Control.

Although patients colonized with MDR microbes can spread worrisome disease, few studies have examined the effect of daily chlorhexidine gluconate (CHG) bathing as part of routine care, the authors, from the University of Wisconsin, said. From May 2010 through January 2011, they screened patients admitted to a 24-bed ICU for MRSA, vancomycin-resistant enterococci, and fluoroquinolone-resistant gram-negative bacilli. They then plotted the monthly incidence and prevalence of colonization of these MDR pathogens.

The scientists found that prevalence of the pathogens decreased immediately after implementing daily CHG bathing and generally remained at that level throughout the study period. Monthly prevalence of colonization with the three MDR organisms ranged from 1.9% to 27.9%.
Apr 18 Am J Infect Control study


Candida bloodstream infections in Peru at times resistant, often deadly

Originally published by CIDRAP News Apr 19

A multicenter study of Candida bloodstream infections in Lima, Peru, yesterday discovered a very high proportion of non-albicans Candida species, a 13% incidence of decreased susceptibility or resistance to fluconazole, and high mortality.

Reporting in PLoS One, Peruvian investigators analyzed data from 158 Candida isolates obtained from 157 patients in three hospitals in Lima from November 2013 to January 2015. Candidemia, or bloodstream infections involving Candida yeast, have been increasing in developing countries, and US officials have recently warned about C auris, an often-resistant and potentially deadly strain that has been increasingly detected.

In the current study, patients' median age was 55, and 24% of infections were in children. Although C albicans typically causes more than half of invasive Candida infections, 72.1% of candidemia in this study was caused by non-albicans strains. Frequency was as follows: C albicans (27.8%), Cparapsilosis (25.3%), C tropicalis (24.7%), and C glabrata (9.5%).

Only 4 isolates were resistant to fluconazole and 17 had reduced susceptibility, for a total of 13.3%.

The researchers also noted that only 28% of patients received appropriate antifungal treatment within 72 hours of diagnosis. The 30-day survival rate was only 60.4%, with treated subjects reaching a 67.4% survival rate and untreated patients a 50.9% rate.

The authors wrote, "It is possible, that the delay in initiating antifungal treatment contributed to the elevated mortality rate, in spite of low antifungal resistance."
Apr 13 PLoS One report


Azithromycin not found to increase risk of ventricular arrhythmia
Originally published by CIDRAP News Apr 18

A study today in the Canadian Medical Association Journal (CMAJ) has found that use of the antibiotic azithromycin was associated with increased risk of ventricular arrhythmia (abnormal heartbeat) when compared with nonuse of antibiotics, but not when compared with use of amoxicillin.

In the nested case-control study, a team of European researchers used healthcare databases from Italy, the United Kingdom, Germany, the Netherlands, and Denmark to identify patients with ventricular arrhythmia who were new antibiotic users. They were looking to see if there is a link between the use of azithromycin—an antibiotic commonly used to treat respiratory and urinary tract infections—and increased risk of death from ventricular arrhythmia. Concerns about a potential link have been raised by the arrhythmogenic risk associated with another macrolide, erythromycin, but observational studies have to date produced conflicting results.

Of the more than 14 million new antibiotic users identified, 12,874 (0.1%) developed ventricular arrhythmia, and 30 were current azithromycin users. In matching the 30 current azithromycin users with 1,344 case controls, the researchers found that, when compared with nonuse of antibiotics, current azithromycin use was associated with an increased risk of ventricular arrhythmia (adjusted odds ratio [OR] 1.97). But when compared with current use of amoxicillin, the increased risk disappeared (adjusted OR 0.94). The results were consistent across separate databases and 1- and 2-stage pooled analyses.

The authors of the study say the decreased risk with an active comparator "suggests significant confounding by indication," meaning that the risk of ventricular arrhythmia is more likely associated with the patient's infection than with the antibiotic being used.

"This finding suggests that the risk of ventricular arrhythmia is more likely to be due to a person's poor health and caused by their infection, rather than to azithromycin itself," study author Gianluca Trifiro, MD, from the University of Messina, Italy, said in CMAJ news release.

The authors note that because the study used data on community use of antibiotics, the findings should not be extrapolated to the hospital setting, where the health status of patients and the nature of antibiotic use are likely to be different.
Apr 18 CMAJ abstract 
Apr 18 CMAJ news release


Study identifies compensatory mutations in multidrug-resistant bacteria

Originally published by CIDRAP News Apr 18

A study today in PLoS Biology suggests that multidrug-resistant bacteria acquire compensatory mutations faster than bacteria that are resistant to a single antibiotic, a finding researchers say could open up new paths for novel antimicrobial strategies.

Chromosomal mutations that confer resistance often come with a fitness cost for bacteria in the absence of antibiotics. To counter that fitness cost, bacteria acquire additional mutations, known as compensatory mutations, that enable them to survive and spread. While this evolutionary process has been studied in single-resistant strains, less is known about how multidrug-resistant bacteria acquire compensatory mutations.

In the study, researchers from the Instituto Gulbenkian de Ciencia in Portugal analyzed and compared, in an antibiotic-free medium, the evolution of strains of Escherichia coli with single resistance to rifampicin and streptomycin and strains with resistance to both antibiotics. What they found was that the low-fitness double-resistant E coli strains acquired compensatory mechanisms faster than the single-resistant strains, primarily because of the acquisition of mutations with larger effects.

In addition, the researchers identified mutations that only compensate for double resistance and likely compensate specifically for the interaction between drug resistances.

"Interestingly, this knowledge may provide new grounds for the development of novel antimicrobial strategies that specifically exploit potential weaknesses derived from epistasis between antibiotic resistances in multidrug-resistant bacteria," the authors write.
Apr 18 PLoS Biol study

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