ASP Scan (Weekly) for Nov 02, 2018

Testing for very resistant TB
;
Antibiotic prescribing in Ontario
;
Antibiotics for COPD
;
MCR resistance genes in Vietnam
;
Cefto-tazo for MDR Pseudomonas
;
Drug-resistant UTIs
;
Hospital antifungal stewardship
;
Carbapenem-resistant Pseudomonas
;
Decline in pediatric Staph, MRSA
;
Candida auris uptick

Study finds pyrosequencing tied to much earlier treatment for MDR-TB

California Department of Public Health (CDPH) investigators found that patients with multidrug-resistant tuberculosis (MDR-TB) had effective treatment begun 5 weeks earlier when pyrosequencing (PSQ) was used to detect resistance mutations than when it was not, according to a study yesterday in Clinical Infectious Diseases.

The CDPH began using PSQ in 2012 to detect mutations associated with resistance to isoniazid, rifampin, quinolones, and injectable drugs in Mycobacterium tuberculosis bacteria. For the study, the researchers used PSQ to test 1,957 specimens collected from Aug 1, 2012, through Dec 31, 2016.

Among 36 patients with MDR-TB who had a sediment specimen submitted for PSQ, the median time from specimen collection to MDR-TB treatment initiation was 12 days—versus 51 days when PSQ was not used. In addition, among 303 TB patients who completed a survey, 126 clinicians (42%) reported PSQ as a reason for treatment change.

The authors conclude, "Survey data suggest clinicians use PSQ to devise effective TB drug regimens. To maximize the benefit of PSQ, earlier submission of specimens should be prioritized."
Nov 1 Clin Infect Dis abstract

 

Study finds wide regional variation in antibiotic prescribing in Ontario

Originally published by CIDRAP News Nov 1

A study yesterday by Public Health Ontario found significant variability by region in outpatient antibiotic prescribing rates in the Canadian province. The findings were published in CMAJ Open,the open-access journal of the Canadian Medical Association.

The cross-sectional study looked at antibiotics dispensed from outpatient retail pharmacies in Ontario from March 2016 through February 2017, with a specific focus on comparing variability across the province's 14 health regions. Outpatient antibiotic use was presented by the number of prescriptions dispensed per 1,000 population.

A total of 8,352,578 prescriptions were dispensed during the 12-month period, or 621 per 1,000 population. Narrow-spectrum penicillins, macrolides, first-generation cephalosporins, and second-generation fluoroquinolones were the most frequently prescribed antibiotic classes. The analysis revealed that while overall variability between the regions was not statistically significant, there was a wide variation between the highest and lowest prescribing regions: from 534 to 778 antibiotics dispensed per 1,000 population. There was minimal change when the rates were adjusted for physician and population characteristics.

The analysis also found significant variability by patient age and sex, with women over 65 receiving 985 antibiotics per 1,000 population and men aged 18 to 64 receiving 441 antibiotics per 1,000 population.

"The research team suspected there was some variability in how often antibiotics were prescribed outside of hospitals and other healthcare institutions, but the level of prescribing was surprising given how much we know about appropriate prescribing, antibiotic resistance and the long-term dangers of excess prescribing," lead author Kevin Schwartz, MD, an infectious disease physician with Public Health Ontario, said in an agency press release.

Schwartz and his co-authors say the data provide an important benchmark for expansion of a provincial outpatient antimicrobial stewardship program.
Oct 31 CMAJ Open study
Oct 31 Public Health Ontario press release

 

COPD reviews highlight some benefits to antibiotics but also precautions

Originally published by CIDRAP News Oct 31

Two Cochrane reviews this week covered the use of antibiotics for chronic obstructive pulmonary disease (COPD), which found benefits in some instances but overall precautions about prescribing them judiciously.

The first review, published Oct 29, focused on COPD flare-ups (exacerbations) and included 2,663 study participants across 19 trials, 11 involving outpatients, 7 with inpatients, and 1 with intensive care unit (ICU) patients.

"Researchers have found that antibiotics have some effect on inpatients and outpatients, but these effects are small, and they are inconsistent for some outcomes (treatment failure) and absent for other outcomes (mortality, length of hospital stay)," the Cochrane reviewers concluded. The study in ICU patients, however, showed a strong beneficial effect of antibiotics.

"These inconsistent effects," the reviewers add, "call for research into clinical signs and biomarkers that can help identify patients who would benefit from antibiotics, while sparing antibiotics for patients who are unlikely to experience benefit and for whom downsides of antibiotics (side effects, costs, and multi-resistance) should be avoided."

The second review, posted yesterday, included 14 studies on prophylactic (preventive) antibiotics for COPD. The studies collectively involved 3,932 patients, mostly frequent exacerbators with at least moderate COPD. Also, the mean age ranged from 65 to 72 years.

The review found that continuous and intermittent prophylactic macrolides reduced COPD exacerbations, while the impact of pulsed antibiotics remains uncertain. The reviewers warn, "Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse."
Oct 29 Cochrane review on COPD flare-ups
Oct 30 Cochrane review on prophylactic therapy

 

Study notes high MCR rates in healthy villagers in Vietnam

Originally published by CIDRAP News Oct 31

More than 80% of Escherichia coli–positive stool specimens collected from healthy people in a village in Vietnam contained the colistin-resistance MCR gene, according to a research letter today in the Journal of Antimicrobial Chemotherapy.

Researchers collected one stool sample each from 98 people living in one of 36 households in a village in Thai Binh province along the northern Vietnamese coast. The villagers ranged in age from 2 to 81 years, with a median of 46.

Of the 98 samples, 88 (89.8%) were positive by culture assay for any pathogen, and 83 (84.7%) were positive for E coli. Of the 83 E coli isolates, 69 (83.1%) tested positive for colistin resistance, 68 of which (81.9%) contained MCR genes. Of that total, 64 were MCR-1, 3 were MCR-3, and one was MCR-1/3. Also, 29 of the 36 households (80.6%) had at least one person harboring an MCR gene.

Colistin is one of the most commonly used antibiotics in chickens and pigs in Vietnam, the authors note. "Such a high amount of colistin consumption by animals in Vietnam may facilitate the wide dissemination of [colistin-resistant E coli] in residents of rural communities," they postulate.

Colistin is considered an antibiotic of last resort for multidrug-resistant infections.
Oct 31 J Antimicrob Chemother letter

 

Benefits noted for ceftolozane-tazobactam for treating MDR Pseudomonas

Originally published by CIDRAP News Oct 31

Ceftolozane-tazobactam for patients with multidrug-resistant (MDR) Pseudomonas aeruginosa illness, known for being a hard-to-treat hospital-acquired infection, is effective, especially when used early, researchers who studied use of the therapy in a multicenter study reported today in Open Forum Infectious Diseases.

For their retrospective study, the investigators collected information on US adults from 20 hospitals who received ceftolozane-tazobactam treatment for MDR Pseudomonas infections from any source for at least 24 hours. Of 205 patients included in the analysis, severe illness and high levels of other medical conditions were common—59% had pneumonia. The team found that delayed treatment was common, with therapy beginning at a median of 9 days after culture collection.

Susceptibility testing found that 125 of 139 (89.9%) of isolates were susceptible to the drug combination. Deaths occurred in 39 (19%) of patients, with clinical success and microbiological cure numbers at 151 (73.7%) and 145 (70.7%), respectively.

Being started on ceftolozane-tazobactam treatment within 4 days of culture collection was associated with survival, clinical success, and microbiological cure.

The researchers said their study is the largest they know of so far to evaluate the treatment combo for MDR Pseudomonas infections. They highlighted the fact that no positive results were seen for concomitant intravenous antibiotics or high-dose ceftolozane-tazobactam treatment, though both practices were common, hinting that monotherapy may be enough for treating susceptible Pseudomonas infections.

They also said the benefit of earlier treatment initiation was significant. "Antimicrobial stewardship programs and individual practitioners alike need to strike a difficult balance between early use of agents such as ceftolozane-tazobactam in appropriate patients who may benefit from it with the economic and microbiological consequences of overuse," they wrote, acknowledging that rapid tests and scoring systems for MDR may help flag patients who could benefit from earlier treatment.
Oct 31 Open Forum Infect Dis abstract

 

Study: Resistant urinary tract infections increase risk of relapse

Originally published by CIDRAP News Oct 30

Researchers with the University of Pennsylvania Perelman School of Medicine have found that community-onset urinary tract infections (UTIs) caused by extended-cephalosporin-resistant Enterobacteriaceae (ESC-R EB) are associated with a sevenfold risk of clinical failure and an increase in inappropriate antibiotic therapy, according to a study today in Infection Control and Hospital Epidemiology.

The retrospective cohort study, conducted at two emergency departments and a network of outpatient practices in the University of Pennsylvania Health System, included all patients who presented with community-onset EB UTIs from December 2010 through April 2013. Exposed patients were identified as those who had an ESC-R EB. They were randomly matched 1:1 with patients who had an ESC-susceptible EB UTI. The primary outcome was clinical failure, defined by repeat clinical visit or phone call for ongoing UTI symptoms.

A total of 302 patients were included in the study, with 151 exposed and 151 unexposed. Within the entire cohort, 86 patients (29%) experienced clinical failure. On multivariable analysis, UTI caused by an ESC-R EB was significantly associated with clinical failure (adjusted odds ratio [aOR], 7.07; 95% confidence interval [CI], 3.16 to 15.82; P < .01). Other independent risk factors for clinical failure included infection with Citrobacter spp and a need for hemodialysis.

The researchers also found that a UTI caused by ESC-R EB was a significant independent risk factor for inappropriate initial antibiotic therapy (IIAT) within 48 hours of UTI evaluation (aOR, 4.40; 95% CI, 2.64 to 7.33; P < .01). They concluded, however, that IIAT was only partially responsible for the worse outcomes associated with ESC-R EB.

"This study adds to the evidence that drug-resistant bacteria are an increasing issue, even in the community and even in patients who have something seemingly uncomplicated, like a urinary tract infection," lead study author and University of Pennsylvania clinical epidemiologist Judith Anesi, MD, said in a press release from the Society for Healthcare Epidemiology of America (SHEA), publisher of the journal. "This is an alarming finding, and interventions to curb antibiotic resistance are urgently needed."
Oct 30 Infect Control Hosp Epidemiol abstract
Oct 30 SHEA press release

 

UK study finds hospital antifungal stewardship reduces costs

Originally published by CIDRAP News Oct 30

An antifungal stewardship (AFS) program centered around specialist input resulted in significant cost savings at a London hospital, with no adverse effects on microbiologic or clinical outcomes, researchers reported today in the Journal of Antimicrobial Chemotherapy.

The AFS program at St. George's Hospital, instituted in October 2010, involves all patients receiving antifungal therapy with amphotericin B, echinocandins, intravenous fluconazole, flucytosine, or voriconazole. All identified patients are seen on a weekly stewardship ward round by an infectious diseases consultant and antimicrobial pharmacist. To determine the effectiveness of the program, researchers collected clinical, microbiologic, and financial outcome data from October 2010 to September 2016.

A total of 432 patients were reviewed 769 times during the study period. The most common drug initiated was amphotericin B (181 patients, 35%), followed by intravenous fluconazole (142 patients, 29%) and echinocandins (120 patients, 23%). In the case of empirical prescribing, 82% (150/183) of patients were subsequently found to have no evidence of invasive fungal infection (IFI). Advice was offered in 64% of reviews (494/769) and was followed in 84% of evaluable recommendations. Of 138 patients prescribed empirical antifungal therapy who had no IFI, 62% had their prescriptions stopped within a week, compared with 44% in a pre-intervention 2009 audit.

Following implementation of the program, annual antifungal expenditure fell by 30%, then increased to 20% above pre-intervention (2009-10) over a 5-year period. But this was a significantly lower rise compared with national antifungal expenditures, which doubled over the same period. Inpatient mortality, Candida species distribution, and rates of resistance were not adversely affected by the intervention.

"In summary, we demonstrate that an AFS program is readily implementable and sustainable over 6 years, offering a large scope for targeted intervention to prevent unnecessary prescribing, with good clinician acceptance and no compromise of clinical outcomes," the authors of the study write.
Oct 30 J Antimicrob Chemother abstract

 

Study examines risk factors for carbapenem-resistant Pseudomonas

Originally published by CIDRAP News Oct 30

In a study yesterday in the Journal of Antimicrobial Chemotherapy, French researchers determined that the risk of acquiring carbapenem-resistant P aeruginosa (CRPA) was associated with carbapenem exposure and with exposure to beta-lactams inactive against P aeruginosa.

The multicenter prospective case–case-control study included 1,808 adults hospitalized in 10 French intensive care units in 2009. Cases were patients with CRPA and patients with carbapenem-susceptible P aeruginosa (CSPA), and controls were patients without P aeruginosa. The researchers investigated antibiotics associated with CRPA isolation and with CSPA isolation after adjusting for non-antibiotic exposures and inpatient characteristics.

Fifty-nine CRPA, 83 CSPA, and 142 control patients were compared. In multivariable analysis, after adjustment for confounders and other non-antibiotic exposures, CRPA cases were independently associated with exposure to carbapenems (odds ratio [OR], 1.205; 95% CI, 1.079 to 1.346) and with exposure to a group of beta-lactams inactive against P aeruginosa (OR, 1.101; 95% CI, 1.010 to 1.201). The antibiotics included amoxicillin, amoxicillin-clavulanic acid, oxacillin, cloxacillin, ertapenem, and first- and second-generation cephalosporins. Conversely, exposure to beta-lactams active against P aeruginosa was an independent protective factor for CSPA isolation (OR, 0.868; 95% CI, 0.722 to 0.976).

The authors of the study hypothesize that the increased risk for CRPA associated with beta-lactams inactive against P aeruginosa may be due to antibiotic selection pressure, with the selection of intestinal flora making the host more susceptible to colonization by resistant strains. They conclude that clinicians should weigh the potential benefits of administering these antibiotics against the increased risk of CRPA infection.
Oct 29 J Antimicrob Chemother abstract

 

Study finds substantial decline in pediatric Staphylococcus infections

Originally published by CIDRAP News Oct 29

Staphylococcus aureus hospitalizations at US pediatric hospitals fell by 36% from 2009 to 2016, with methicillin-resistant S aureus (MRSA) declining by 52%, with a corresponding drop in antibiotic use, according to a study today in Infection Control and Hospital Epidemiology.

The retrospective cohort study was conducted at 39 US pediatric hospitals using the Pediatric Health Information Systems administrative database and was limited to patients under 18 years of age who had an S aureus infection indicated in the electronic medical record. Annual rates for S aureusoverall, MRSA, and methicillin-susceptible S aureus (MSSA) were calculated per 1,000 admissions.

Among the 39 hospitals, investigators identified 116,152 S aureus hospitalizations from 2009 to 2016. During the period, the annual S aureus rate fell from 26.3 to 16.8 infections per 1,000 admissions (P< .001), with MRSA decreasing from 14.4 to 6.9 infections per 1,000 admissions (P < .001) and MSSA infections falling 17% (from 11.9 to 9.9 infections per 1,000 admissions; P < .001). The proportion of S aureus infections that were MRSA dropped from 55% in 2009 to 41% in 2016. In addition, days of therapy for anti-MRSA antibiotics declined from 38.0 to 24.4, with the most notable decreases for clindamycin (14.32 to 7.5) and vancomycin (16.6 to 10.8).

The authors of the study suggest that a number of factors may contribute to the decreases, including earlier recognition of S aureus infections and initiation of appropriate therapy in outpatient settings, but they say more research is needed to fully understand what's driving the epidemiologic changes.
Oct 29 Infect Control Hosp Epidemiol abstract

 

US Candida auris cases continue to rise

Originally published by CIDRAP News Oct 29

The number of confirmed and probable cases of Candida auris in the United States has jumped to 463, according to the latest update from the Centers for Disease Control and Prevention (CDC), up from 349 in July.

As of Sep 30, infections caused by the multidrug-resistant fungus have been identified in 11 states, with the vast majority of confirmed cases reported in New York (239), New Jersey (94), and Illinois (80). Cases have also been reported in Massachusetts (7), Florida (4), Maryland (3), Oklahoma (2), California (1), Connecticut (1), Indiana (1), and Texas (1). Of the 463 clinical cases identified, 433 are laboratory-confirmed and 30 are listed as probable.

The CDC also said that targeted screening in six states with clinical cases has identified an additional 801 patients who are colonized with C auris. The screening is being conducted as part of an effort to control the spread of the fungus, which can persist on surfaces in healthcare facilities and spread between patients.

Originally identified in Japan in 2009, C auris has caused outbreaks in healthcare settings in more than 20 countries and has shown resistance to the three major classes of antifungal drugs used to treat Candida infections. In patients with compromised immune systems, it can cause serious invasive infections affecting the bloodstream, heart, brain, ear, and bones. The CDC estimates that 30% to 60% of patients with invasive C auris infections have died.

C auris was made a nationally notifiable condition at the 2018 Council for State and Territorial Epidemiologists annual conference in August. 
Oct 23 CDC C auris case count page

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