ASP Scan (Weekly) for Nov 10, 2017

Antibiotics and subsequent sepsis
MCR surveillance in California
Community-related C diff
Antibiotic sparing for UTIs
More-resistant MDR-TB
MDR-TB in Minnesota
Strep burden, resistance threat

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

Increased sepsis risk found in patients previously treated with antibiotics

Originally published by CIDRAP News Nov 9

A significant increase in cases of severe sepsis and septic shock within 90 days of hospital discharge was observed among patients exposed to antibiotics during their previous hospital stay, researchers with the Centers for Disease Control and Prevention reported today in Clinical Infectious Diseases.

For the study, the researchers obtained hospital discharge and drug use data from a large database that contains billing records from more than 500 US hospitals. They included hospital admissions for all patients discharged during two periods: January 2007 through September 2010 and January 2011 through September 2014. The purpose was to examine the association between the use of certain antibiotics during the initial hospital stay and the risk of post-discharge sepsis, using a multivariable logistic regression model that controlled for potential confounding factors. The antibiotics were categorized into high-risk, low-risk, and control categories, based on association with clinically important microbiome disruption.

Among 516 hospitals, the researchers randomly selected more than 12 million patients who had a hospital stay during the study period and identified 21,247 (0.17%) who had severe sepsis or septic shock during within 90 days of their index stay. Among patients with exposure to a high-risk antibiotic agent—including third- and fourth-generation cephalosporins, fluoroquinolones, licnosamides, beta-lactam/beta-lactamase inhibitor combinations, oral vancomycin, and carbapenems—during the index stay, the proportion of patients with severe sepsis post-discharge was 0.3%, compared with 0.1% of patients with no antibiotic exposure.

In the multivariable logistics regression model, exposure to a high-risk antibiotic was associated with a 65% increased risk of severe sepsis within 90 days of discharge (odds ratio [OR], 1.65). Exposure to low-risk and control antibiotics were not as strongly associated with severe sepsis (OR, 1.07 and OR, 1.22, respectively). Patients exposed to four or more antibiotic classes or more than 14 days of antibiotic therapy had over twice the risk of severe sepsis (OR, 2.23 and OR, 2.17, respectively).

The authors say the findings support the hypothesis that microbiota disruption is associated with an increased risk of severe sepsis post-hospital discharge. They also argue that the study makes a case for increased antibiotic stewardship, given that 30% to 50% of antibiotic use in hospitals is estimated to be inappropriate. "This study builds on a growing evidence base suggesting that increased stewardship efforts in hospitals may not only prevent antimicrobial resistance, CDI [Clostridium difficile infection] and other adverse effects, but also reduce other unwanted outcomes potentially related to disruption of the microbiota, including sepsis," they write.
Nov 9 Clin Infect Dis study 


Study finds no MCR genes in Shiga toxin–producing E coli in California

Originally published by CIDRAP News Nov 9

Molecular screening of 1,000 Shiga toxin–producing Escherichia coli (STEC) isolates from an agricultural region in California detected no colistin resistance genes, investigators from the US Department of Agriculture reported yesterday in PLoS One.

The STEC isolates were recovered from livestock, wildlife, produce, and other environmental sources in California's central coast from 2006 through 2014. They included STEC O157 and non-O157. STEC is recognized as the leading cause of foodborne illness outbreaks in the United States.

The investigators screened the isolates for the presence of MCR-1 and MCR-2, the plasmid-mediated colistin-resistance genes that were first identified in Chinese pigs in 2016 and since then have spread around the world. Recent studies have found the presence of MCR-1 in some STEC isolates.

The results obtained via polymerase chain reaction (PCR) testing showed that all 1,000 STEC isolates were negative for MCR genes, a finding that suggests "a very low probability" that MCR genes are prevalent in STEC recovered from the region. The authors say the findings also indicate a lower prevalence of transferable colistin resistance in the United States when compared with other countries, especially those where colistin use in food-producing animals has been uncontrolled.
Nov 8 PLoS One study


VHA study notes rise in community-associated C diff infections

Originally published by CIDRAP News Nov 8

A study of Veterans Health Administration (VHA) hospitals has found that cases of community-associated Clostridium difficile infection (CA-CDI) are on the rise, researchers from the University of Texas at Austin reported yesterday in the American Journal of Infection Control.

In the retrospective cohort study of all adult VHA beneficiaries with CDI from October 2002 through September 2014, the researchers identified 30,326 patients with a first CDI episode during the 12-year period. Health care facility–onset CDI (HCFO-CDI) accounted for 60.2% of cases and was the predominant type. Among cases linked to the community, 20.6% were classified as community-onset HCFO-CDI (CO-HCFA-CDI), and 19.2% were classified as CA-CDI.

There was a shift from HCFO-CDI to CA-CDI over the study period. The proportion of patients with HCFO-CDI decreased from 73.5% during fiscal year (FY) 2003 to 53.2% during FY 2014, while CA-CDI increased from 8.3% to 26.7%.

HCFO-CDI patients, however, had worse outcomes. In multivariable models, HCFO-CDI was a positive predictor of severe CDI (odds ratio [OR], 1.71) 30-day mortality (OR, 1.46), 60-day mortality (OR, 1.48), and 90-day mortality (OR, 1.54), but was not predictive of 30-day recurrence (OR, 0.41), 60-day recurrence (OR, 0.40), and 90-day recurrence (OR, 0.41).

The authors of the study suggest the shift from HCFO-CDI to CA-CDI over the 12-year period could be caused by increasing use of high-risk antibiotics, such as fluoroquinolones, in the community, as well as increasing use of proton-pump inhibitors. They also cite an increase in the number of elderly patients admitted to long-term care facilities, which have been identified as reservoirs of CDI.
Nov 7 Am J Infect Control study


Swiss study finds NSAIDS inferior to antibiotics for treating UTIs

Originally published by CIDRAP News Nov 8

A randomized controlled trial by Swiss researchers has found that symptomatic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) as a potential antibiotic stewardship step is inferior to antibiotic treatment in women who have uncomplicated urinary tract infections (UTIs) and is likely to be associated with increased risk of pyelonephritis.

In a study today in BMJ, the researchers randomly assigned 253 women with uncomplicated lower UTI 1:1 to treatment with diclofenac or norfloxacin. Both patients and assessors were blinded to allocation. Participants started treatment immediately after randomization and were advised to take two capsules per day. The primary outcome was symptom resolution on day 3, and the secondary outcome was the use of any antibiotic up to day 30. All participants were given a package of fosfomycin to take as a rescue antibiotic if symptoms persisted past day 3.

Resolution of symptoms at day 3 was observed in 72 (54%) of 133 women assigned to diclofenac and 96 (80%) of 120 of women assigned to norfloxacin (risk difference, 27%, P = 0.98 for non-inferiority). The median time until resolution of symptoms was 4 days in the diclofenac group and 2 days in the norfloxacin group. A total of 82 women (62%) in the diclofenac group and 118 (98%) in the norfloxacin group (98%) used antibiotics up to day 30 (risk difference, 37%, P < 0.001 for superiority). Six women in the diclofenac group received a diagnosis of pyelonephritis—a bacterial infection of the kidneys—compared with none in the norfloxacin group (P = 0.03).

Although the results show that symptomatic treatment with NSAIDs is inferior to antibiotic treatment for UTI symptom relief, the authors of the study say the fact that fewer women in the diclofenac group were on antibiotics until day 30 is important. "The observed clinically relevant reduction in antibiotic use, which would likely contribute directly to decreasing resistance rates in the affected population, suggests that alternative approaches of combining symptomatic treatment with deferred, selective antibiotic use should be developed and tested in future trials," they write. 
Nov 8 BMJ study


Most MDR-TB isolates in central China resistant to key MDR-TB drug

Originally published by CIDRAP News Nov 7

Chinese scientists have found that 62% of multidrug-resistant tuberculosis (MDR-TB) isolates they tested were also resistant to pyrazinamide (PZA), a key drug in treating MDR-TB, according to a study published yesterday in BMC Infectious Diseases.

The researchers analyzed 133 MDR-TB isolates collected from TB patients in Chongqing province in central China. They assessed for PZA resistance using a Bactec MGIT 960 system and then sequenced genes that conferred PZA resistance.

They found that 83 (62.4%) of the 133 isolated were PZA-resistant. In addition, resistance to streptomycin, ofloxacin, kanamycin, amikacin, and capromycin were more frequently observed among PZA-resistant isolates compared with PZA-susceptible isolates. And sequence analysis revealed that 73 (88.0%) of the MDR strains harbored a mutation located in the pncA gene.

PZA is typically subscribed in both first- and second-line treatments of MDR-TB.
Nov 6 BMC Infect Dis study


Minnesota officials report deadly 17-case outbreak of MDR-TB

Originally published by CIDRAP News Nov 6

Ramsey County, Minnesota, home to St. Paul, is combatting the nation's largest outbreak of MDR-TB, which has grown to 17 cases and 6 deaths, the Minneapolis Star Tribune reported today.

The outbreak has primarily affected elderly residents of the county's Hmong community, with 10 cases linked to a senior care center, where the first case was detected last year. Four other Ramsey County Hmong residents also contracted MDR-TB.

Of the 6 deaths, 3 were a direct result of the disease, health officials said. State officials are monitoring more than 350 people who may have been exposed. Testing on 125 people has revealed 58 latent TB cases, which means people who have no symptoms but can pass the disease to others. The report did not say whether those cases involved resistant strains. People with latent TB are being urged to take second-tier antibiotics—the same as MDR-TB patients—but the treatment can last up to 2 years and cost $134,000. (First-line treatment lasts at least 6 months and costs $17,000, the story said.)

"In the case of these individuals, if there wasn't evidence that they had been exposed to multi-drug resistant tuberculosis, then they would have just been recommended to get the normal course of treatment," said Kris Ehresmann, RN, MPH, infectious disease director at the Minnesota Health Department. "But the [second-tier] treatment is arduous and has many side effects."

The outbreak represents another costly challenge for Minnesota health officials, who had to deal with a 79-case measles outbreak earlier this year. The state has tapped almost $225,000 in emerging fund to combat the MDR-TB outbreak.

Minnesota has the second-largest US Hmong population, after California.
Nov 6 Star Tribune story


Supplement details group B Streptococcus, resistance risks

Originally published by CIDRAP News Nov 6

Group B Streptococcus (GBS) bacteria cause at least 147,000 stillbirths and infant deaths worldwide each year, but providing effective treatment brings up antibiotic resistance and stewardship issues, according to a supplement to Clinical Infectious Diseases published today.

Led by the London School of Hygiene & Tropical Medicine (LSHTM) and involving more than 100 researchers from around the world, the series of 11 research papers estimates that about 18% of women globally harbor GBS. The researchers also conservatively estimate that, out of 410,000 GBS cases every year, at least 147,000 stillbirths and infant deaths occur around the globe annually. Africa had the highest burden, with 54% of estimated cases and 65% of stillbirths and infant deaths, despite housing only 13% of the world's population.

According to the new research, funded by the Bill & Melinda Gates Foundation, the top five countries by numbers of pregnant women colonized with GBS were India (2,466,500), China (1,934,900), Nigeria (1,060,000), the United States (942,800), and Indonesia (799,100).

GBS prevention focuses on prescribing antibiotics to women in labor, aiming to reduce disease in infants, given that no vaccine is available, according to an LSHTM news release. At least 60 countries have a policy for antibiotic use in pregnancy to prevent newborn GBS disease, but implementation of policies varies.

Joy Lawn, MB BS, PhD, an LSHTM professor, said in the release, "Antibiotics currently prevent an estimated 29,000 cases of early-onset group B Streptococcal disease per year, almost all in high-income settings. However, this approach may be difficult in low-income settings where many births take place at home, and laboratory capacity for screening for GBS is limited. In addition, giving antibiotics to 21.7 million women may contribute to antimicrobial resistance—a major global health crisis."
Nov 6 Clin Infect Dis supplement
Nov 6 LSHTM 
news release

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