ASP Scan (Weekly) for Feb 22, 2019

Antibiotic Rx for skin infections
MCR-1, MCR-3 hybrid E coli
XDR gonorrhea clone
New metallo-beta-lactamase
Fast track for pneumonia antibiotic
Nursing home UTI stewardship
Triclosan-induced antibiotic tolerance
Staph clindamycin resistance
Resistant bacteria in farm soil
Geographic MRSA risks
Readmission after C diff

Nursing home survey highlights antibiotic overuse for skin infections

A study today in Epidemiology and Infection reports that less than a third of the residents in Australian nursing homes who were prescribed an antimicrobial for a skin infection had a confirmed bacterial infection.

The data come from the Aged Care National Antimicrobial Prescribing Survey, a structured point-prevalence survey of Australian nursing homes conducted from June to September 2017. The researchers focused on skin and other soft-tissue infections (SSTIs), because findings from previous surveys have indicated that SSTIs are the second most common infection among nursing home residents. Data collected about antimicrobials prescribed on the survey day included clinical indication, rationale, route, frequency, and duration.

Of the 12,319 surveyed residents from 292 aged care facilities, 452 (3.7%) were prescribed an antimicrobial for an SSTI. The most frequently reported clinical indications among residents were cellulitis, soft tissue or wound infection (n = 130), followed by fungal skin infection (60), conjunctivitis (49) and oral candidiasis (18). Confirmed infection was documented in only 29% of cases. Topical clotrimazole was most frequently prescribed, often for unspecified indications. Where an indication was documented, antimicrobial choice was generally aligned with recommendations.

"While targeted antimicrobial prescribing is generally aligned with national recommendations, we observed a large proportion of prescribed antimicrobial agents to be for unspecified clinical indications," the authors of the study write. "Methods to enhance clinician documentation of indications for antimicrobial therapy are required, and development of standardised tools for assessing appropriateness of antimicrobial agents in elderly populations would support these interventions."
Feb 22 Epidemiol Infect abstract


Chinese researchers report MCR-1, MCR-3 resistance genes together

Chinese scientists have identified a novel hybrid plasmid with both MCR-1 and MCR-3 colistin-resistance genes from an Escherichia coli isolate, they noted yesterday in the Journal of Antimicrobial Chemotherapy.

The isolate was obtained from pig manure in Sichuan province. Via whole-genome sequencing and other tests, the scientists identified both MCR-1 and MCR-3.19 on a single plasmid, which are mobile segments of DNA that can transfer resistance genes to other pathogens, including non–E coli microbes. Colistin is a last-resort antibiotic used against multidrug-resistant bacteria.

The genetic structure of the two genes was similar to those found previously in plasmids. The researchers also identified three other plasmids in the isolate, two of which harbored resistance genes.

"This finding suggested that evolution of mcr genes among various plasmids was being driven by mobile elements," the authors conclude. "Molecular surveillance of mcr gene co-occurrence warrants further investigation to evaluate the public health risk."
Feb 21 J Antimicrob Chemother abstract


Genomic analysis shows UK, Australian XDR gonorrhea cases are related

Originally published by CIDRAP News Feb 21

An international team of scientists reported today in Eurosurveillance that the three extensively drug-resistant (XDR) gonorrhea cases identified in Australia and the United Kingdom in 2018 were caused by a single XDR clone.

The three cases, which were identified in February, March, and April 2018, all displayed ceftriaxone resistance and high-level azithromycin resistance, a combination that had not previously been reported. Dual therapy with ceftriaxone and azithromycin is the first-line treatment for gonorrhea.

The UK case involved a man who reported sexual contact with a woman in Thailand; the Australia cases included a man who reported having sex with a woman in Southeast Asia and a woman with no travel history outside of Australia.

Genomic analysis of four isolates (two from the UK case, one each from the Australia cases) revealed that all four shared the same Neisseria gonorrhoeae multi-antigen sequence type (ST 16848), multilocus sequence type (ST 12039) and NG-sequence typing for antimicrobial resistance type (NG-STAR 996), and all harbored the same ceftriaxone resistance–conferring penA allele and copies of the genetic mutation responsible for high-level azithromycin resistance. 

Phylogenetic analysis showed that the sequences from the two UK isolates and the isolate from the Australian woman were indistinguishable, and separated from the male Australian case by one single nucleotide polymorphism. These findings suggest the three cases are highly related and of the same gonococcal clone, which the authors of the study named A2543. They warn that the clone could be present elsewhere, but may not have been detected because of a lack of testing and surveillance. 

"The isolation of these A2543 clone XDR gonococci within a short time period, with epidemiological links to south-east Asia in two of three cases, suggests that this clone may be circulating in Asia, which is concerning," they write. "Further spread of this A2543 XDR strain would have serious implications for the current first-line NG treatment recommendations."
Feb 21 Eurosurveill rapid communication


Canadian researchers report novel metallo-beta-lactamase gene, CAM-1

Originally published by CIDRAP News Feb 21

Canadian scientists report identifying a novel metallo-beta-lactamase gene, CAM-1, which confers resistance to the antibiotic carbapenem, in clinical Pseudomonas aeruginosa isolates, according to data published yesterday in the Journal of Antimicrobial Chemotherapy.

Using whole-genome sequencing, the researchers analyzed four clinical isolates of P aeruginosa from three patients hospitalized in Alberta in 2008 and 2009 that were negative by polymerase chain reaction for KPC, OXA-48, NDM, VIM, IMP, GES, and NMC/IMI carbapenemase genes. They used bioinformatic analysis; cloning, antimicrobial susceptibility testing, and biochemical and phenotypic characterization; and single-nucleotide variant typing to further assess the isolates.

The group, which included scientists from the Public Health Agency of Canada, called the novel gene Central Alberta Metallo-beta-lactamase, or CAM-1. The gene conferred carbapenem resistance to an E coli TOP10 strain but could not be transferred by conjugation.

The authors said no additional CAM-1 genes have been identified in the province in more recently hospitalized patients.
Feb 20 J Antimicrob Chemother report


FDA approves New Drug Applications for Nabriva's pneumonia antibiotic

Originally published by CIDRAP News Feb 21

Nabriva Therapeutics of Dublin announced that the US Food and Drug Administration (FDA) has accepted its New Drug Applications (NDAs) and granted priority review for both the oral and intravenous (IV) formulations of lefamulin, a first-in-class, semi-synthetic pleuromutilin antibiotic for treating community-acquired bacterial pneumonia (CABP).

The goal date for the completion of the FDA's review is Aug 19. In addition to authorizing priority review, the FDA has also granted lefamulin Qualified Infectious Disease Product and fast-track designations.

Jennifer Schranz, MD, Nabriva's chief medical officer, said in a company news release. "We believe lefamulin has the potential to provide a much-needed monotherapy treatment option for adults with CABP. As demonstrated in our clinical program, the ability to switch from IV to oral administration and the short-course oral regimen has the potential to position lefamulin, if approved, as a monotherapy option for patients in the hospital, transition of care and ambulatory care settings."

The company said the two NDAs are supported by two phase 3 clinical trials—known as LEAP 1 and LEAP 2—that evaluated the safety and efficacy of IV and oral lefamulin compared with moxifloxacin in adults with CABP, including the option to switch from IV to oral administration and a short course of oral treatment with lefamulin. "In both LEAP 1 and LEAP 2, lefamulin was demonstrated to be non-inferior to moxifloxacin, and met both the FDA and European Medicines Agency (EMA) primary and secondary efficacy endpoints for the treatment of CABP," the company said.

Lefamulin was also generally well tolerated in the trials. Nabriva plans to submit a marketing authorization application for lefamulin in Europe in the first quarter of 2019.
Feb 19 Nabriva news release
Dec 21, 2018, CIDRAP News scan on NDA application


Nursing home stewardship program focuses on undocumented UTIs

Originally published by CIDRAP News Feb 20

An antimicrobial stewardship intervention targeted to rural nursing homes in Alberta, Canada, significantly decreased the level of urine culture testing and antibiotic prescribing without an increase in hospitalization or mortality, Canadian researchers reported today in Infection Control and Hospital Epidemiology.

Given concerns about antimicrobial overprescribing in nursing home residents who don't meet the clinical criteria for urinary tract infections (UTIs), the investigators examined the impact of an intervention focused on urine testing and appropriate treatment.

The study spanned 42 nursing homes from April 2015 through January 2016, with 21 intervention sites receiving staff education, physician small-group academic detailing sessions, and integrated clinical decision-making tools. Patients at control sites received standard care. The researchers collected data on urine culture testing, antibiotic prescribing, and clinical outcomes 6 months before and 12 months after the stewardship intervention.

The team found statistically significant decreases in the rate of urine culture testing and antibiotic prescribing in the intervention group: -2.1 tests per 1,000 resident days (95% confidence interval [CI], -2.5 to -1.7, P < .001) and -0.7 prescriptions per 1,000 resident days (95% CI, -1.0 to -0.4, P < .001). Researchers estimated that over a year at a 40-bed nursing home, the intervention would result in 31 fewer urine cultures and 10 fewer antimicrobial prescriptions.

"Admissions to acute-care facilities or emergency departments or mortality between the groups did not increase, indicating that reducing antimicrobial therapy did not cause harm," the team wrote. They added that the concepts were well accepted by physicians and other staff members, with reassurances that limiting testing and antibiotic prescribing to those with UTI clinical suspicion would not be harmful.
Feb 20 Infect Control Hosp Epidemiol abstract


Study: Triclosan lowers antibiotic efficacy in culture, mouse tests

Originally published by CIDRAP News Feb 20

A new study by researchers with Washington University in St. Louis has found that clinically relevant concentrations of triclosan, an antimicrobial used in a wide range of consumer products, significantly increased bacterial tolerance to antibiotics in vitro and reduced antibiotic efficacy in a mouse urinary tract infection model. The findings appeared yesterday in Antimicrobial Agents and Chemotherapy.

To assess whether physiologically relevant levels of triclosan are sufficient to promote tolerance to bactericidal antibiotics, the researchers cultured E coli and methicillin-resistant Staphylococcus aureus (MRSA) in amounts of triclosan similar to the concentration found in the urine of individuals who use triclosan-containing products, then exposed the bacteria to high concentrations of antibiotics. The results showed that triclosan had a dramatic protective effect for the microbes, increasing E coli and MRSA tolerance to the antibiotics as much as 10,000-fold.

To determine whether the tolerance observed in vitro was relevant in vivo, the researchers tested the impact of triclosan on mice with E coli urinary tract infections. In mice with levels of triclosan similar to those reported in human urine, the efficacy of ciprofloxacin was reduced up to 100-fold.

The authors of the study note that although the FDA banned the use of triclosan in household soap in 2017, other countries have not taken similar action, and the compound is still used in a variety of other consumer products. Approximately 75% of US adults have detectable levels of triclosan in their urine, and as many as 10% have concentrations that are equal to or greater than the minimum inhibitory concentration levels for E coli and MRSA.

"These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds," they write.
Feb 19 Antimicrob Agents Chemother abstract


Study notes increase in clindamycin resistance in surgical-site infections

Originally published by CIDRAP News Feb 20

In a research brief today, scientists from Johns Hopkins and the Center for Disease Dynamics, Economics and Policy (CDDEP) report a significant increase in clindamycin resistance in Staphylococcus aureus isolates from surgical-site infections (SSIs).

The retrospective study included all S aureus isolates from SSIs in adult patients at Johns Hopkins Hospital from Jan 1, 2012, through Dec 1, 2017. Among the 109 cultures, clindamycin resistance increased from 20% in 2012 to 38% in 2017 (P < .01), while resistance to tetracycline decreased significantly, from 20% to 0%, during the same period. Trimethoprim-sulfamethoxazole resistance remained relatively stable, increasing from 10% in 2012 to 13% in 2017, while erythromycin resistance decreased from 40% to 29%.

Of 68 cases with available SSI prophylaxis and allergy data, 13 (20%) had a reported penicillin allergy. Also, 5 of these patients received clindamycin even though only 1 had a high-severity reaction on record. Of the 5 patients who received clindamycin, 2 developed a clindamycin-resistant S aureus SSI.

The authors conclude, "Increasing clindamycin resistance in SSIs [S aureus] raises concerns about its use as an alternative surgical prophylaxis agent." They add that improving penicillin allergy documentation and considering alternatives to clindamycin could reduce such cases.
Feb 20 Infect Control Hosp Epidemiol extract


Resistance genes found in soil 2 years after cattle operation ceases

Originally published by CIDRAP News Feb 18

A new study led by scientists from US Department of Agriculture (USDA) found that antibiotic resistance genes persist in a beef cattle environment even 2 years after cessation of operations.

Writing in PLOS One, researchers from the USDA and Western Kentucky University (WKU) in Bowling Green collected soil samples from both the feedlot and gracing areas of a WKU beef cattle operation before the cattle were removed and then 1 and 2 years after cattle removal. They measured total bacterial populations, total Enterococcus species, integrons, and antimicrobial resistance genes (ARGs) against erythromycin, sulfonamide, and tetracycline.

The investigators noted that concentrations of total bacteria, Enterococcus species, class 1 integrons, and ARGs were higher in the feeding area and around the fence and gate that led to the grazing area but declined gradually followed a gradual decline across the grazing area. They also reported that, although concentrations of total bacteria, Enterococcus species, and ARGs in the feeding area significantly decreased 2 years after cattle removal, their concentrations were still detected, and, again, at higher levels than observed in the grazing area.

The highest concentrations were found around feeding and watering areas.

The authors conclude, "Higher concentrations over two years in the feeding area when compared to the grazing area suggest a lasting effect of confined beef cattle production system on the persistence of bacteria and ARGs in the soil."
Feb 15 PLOS One study


Study: Race, household crowding linked to higher risk for CA-MRSA

Originally published by CIDRAP News Feb 18

A study today using geocoded electronic health record (EHR) data to identify risk factors and characterize geographic variations of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) rates in children in Atlanta has found that neighborhoods with higher proportions of black residents, household crowding, and children under the age of 4 have the greatest risk of infection, researchers reported in BMC Infectious Diseases.

The retrospective study looked at children in the Atlanta metropolitan statistical area who were treated for S aureus infection at two hospitals from 2002 through 2010. Children met the case definition if their EHR reported a positive MRSA infection on the first culture test during a single hospitalization. A generalized estimated equations model was developed, and crude and adjusted odds ratios (aOR) were based on S aureus risks.

The researchers measured the risk of S aureus as standardized incidence ratios (SIRs) calculated within aggregated US 2010 Census tracts called spatially adaptive filters, and then created maps that differentiate the geographic patterns of antibiotic-resistant and non-resistant forms of S aureus.

Overall the analysis found 10,642 S aureus cases, with 5,379 MRSA and 5,263 methicillin-susceptible S aureus (MSSA) infections. CA-MRSA rates increased at higher rates compared with non-resistant forms (P = 0.01), and infections more than doubled during the study period, from 23.2% in 2002 to 53.7% in 2006. Black children were almost 1.5 times as likely as white children to have CA-MRSA infections (aOR, 1.58; 95% confidence interval [CI], 1.44 to 1.75, P < 0.0001); this finding persisted at the block group level (P < 0.001) along with household crowding (P < 0.001). Children younger than 4 years also had increased risk for CA-MRSA (aOR, 1.65: 95% CI, 1.48 to 1.83, P < 0.0001).

The spatial analysis showed that CA-MRSA infections encompassed larger areas with higher SIRs compared to non-resistant forms and were found in block groups with higher proportions of black residents (r = 0.517, P < 0.001), younger children (r = 0.137, P < 0.001), and crowding (r = 0.320, P < 0.001). Over 75% of the CA-MRSA cases were found in Fulton and DeKalb counties, which are two of the most densely populated counties in Georgia.

"This study demonstrates how geocoded EHR data can be used to identify areas of excess risk for S. aureus infections, which is important for developing interventions to prevent the spread of antibiotic resistant infectious conditions," the authors of the study write. "These methods can be used to identify specific areas to target public health intervention strategies."
Feb 18 BMC Infect Dis study


Hospital readmission common after C difficile infection, study finds

Originally published by CIDRAP News Feb 18

An analysis of nationwide US data has revealed that one in five patients admitted with Clostridioides difficile infection (CDI) is readmitted within 30 days, with almost half because of infections and the leading cause being repeat CDI, according to a study in the American Journal of Infection Control.

The researchers studied details on 38,409 patients admitted to a hospital with a primary diagnosis of CDI, according to 2013 data from the Nationwide Readmissions Database. The mean age was 67.6, 65.0% were women, and 44.7% had two or more comorbidities.

Of the 38,409 patients initially admitted for CDI, 8,198 (21.3%) were readmitted to the hospital within 30 days. Of these, 2,206 (26.9%) were readmitted with CDI as the primary diagnosis, which accounted for 5.7% of all patients initially admitted with CDI. Other leading causes were non–C difficile septicemia (11.6%), congestive heart failure (3.6%), urinary tract infection (3.2%), and diarrhea (2.5%).

Being female and having either renal disease or anemia were associated with increased CDI readmission risk, as was being discharged home versus another healthcare facility.

The authors conclude, "This information may provide a framework for hospitals to develop increased awareness of at-risk populations. Further studies can be aimed at evaluating the role of new therapies on cost and readmission."
Feb 16 Am J Infect Control abstract

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