Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Lyme disease study finds frequent misdiagnosis, unnecessary antibiotics
Data from a single-center study indicate widespread misdiagnosis of Lyme disease and unnecessary antibiotic treatment, particularly among those with unexplained symptoms lasting longer than 3 months, a team of US researchers reported today in Open Forum Infectious Diseases.
In the retrospective study, researchers reviewed data on patients referred to an outpatient infectious disease clinic of the Johns Hopkins University School of Medicine for Lyme disease consultation from 2000 through 2013 and analyzed diagnoses and treatments. They then compared clinical characteristics of those with Lyme disease and those who were misdiagnosed to evaluate variables that could be useful for predicting when Lyme disease would not account for consultation complaints.
Of the 1,261 patients included in the study, 911 (72.2%) did not have Lyme disease, 184 (14.6%) had active/recent Lyme disease, 150 had (11.9%) had remote Lyme disease, and 16 (1.3%) had possible Lyme disease. Multivariable analysis showed that patients without Lyme disease were more likely to be female (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.08 to 2.25), have symptoms for more than 3 months (OR, 8.78; 95% CI, 5.87 to 13.1), have higher symptom counts (OR per additional symptom, 1.08; 95% CI, 1.02 to 1.13), have more Lyme-related laboratory testing (OR per additional laboratory test, 1.17; 95% CI, 1.03 to 1.32), and to have been diagnosed with what were regarded as co-infections (OR, 3.13; 95% CI, 1.14 to 8.57).
Of the 911 patients without Lyme disease, 764 (83.9%) received antimicrobials to treat Lyme disease or their co-infections. In addition, 53.4% of patients received antibiotics for longer durations than recommended regardless of their diagnosis. The percentage of patients established to have Lyme disease was lower than in earlier studies of referred populations.
The authors of the study say the findings suggest that Lyme disease appears to be an attractive diagnosis for otherwise unexplained, longstanding problems that are referred to by some as "chronic Lyme disease," a term that does not have consensus medical definition.
"This thirteen-year study suggests that patients and clinicians may be influenced by alternative, non-evidence-based medical practices, or could be confused by non-validated laboratory test results or interpretations," they write.
Jul 5 Open Forum Infect Dis abstract
Study: Gut persistence could aid spread of pandemic urinary E coli clones
A study yesterday in Clinical Infectious Diseases indicates that two pandemic, uropathogenic Escherichia coli strains have the ability to persist in the gut and cause bacteriuria in healthy women.
In an analysis of 1,031 fecal samples from women with no documented urinary tract infection (UTI), researchers from the University of Washington School of Medicine found that 88.8% (916 samples) contained E coli and 8.8% (91 samples) yielded fluoroquinolone-resistant E coli isolates. Among these isolates, 14 distinct clonal types were identified, with E coli ST131-H30R and ST1193—the two most dominant multidrug-resistant E coli clonal types found in patients with suspected UTIs—being the most prevalent. Follow-up urine samples in 74 of the women showed that ST131 H30R and ST1193 were isolated nearly twice as frequently as fluoroquinolone susceptible E coli and other clonal types of fluoroquinolone-resistant E coli.
Out of 67 women who provided both a urine sample and a second fecal sample, there was a strong association between bacteriuria and fecal persistence (OR, 8.3; 95% CI, 1.5 to 22.2, P = .011).
The researchers say the superior gut persistence of the pandemic clones, and their superior capability to invade the urinary tract, could contribute to their remarkable global spread and their dominance among fluoroquinolone-resistant E coli of UTI origin.
Jul 4 Clin Infect Dis abstract
Multistate outbreak of multidrug-resistant Salmonella sickens 45
Originally published by CIDRAP News Jul 3
The Centers for Disease Control and Prevention (CDC) said today that it is investigating a multistate outbreak of multidrug-resistant Salmonella infections with suspected links to contact with pig-ear dog treats.
The CDC said that 45 people in 13 states have been infected with the outbreak strain of Salmonella I 4,[5],12:i:-, and 12 have been hospitalized. No deaths have been reported. Ill people range in age from 1 year to 81 years.
Whole-genome sequencing of isolates from 30 of the infected people predicted antibiotic resistance or decreased susceptibility to ampicillin, ciprofloxacin, gentamicin, nalidixic acid, streptomycin, sulfisoxazole, tetracycline, and trimethoprim sulfamethoxazole.
In interviews, 34 of 38 ill people indicated contact with a dog before getting sick, and 17 of 24 people with available information reported contact with pig-ear dog treats or with dogs who had been given the treats.
In Michigan, sampling of pig-ear dog treats from retail locations where ill people reported buying the products detected several Salmonella strains, but not the outbreak strain. A common supplier of the treats has not been identified.
The affected states are Iowa, Michigan, Kansas, Missouri, Illinois, Indiana, Wisconsin, North Dakota, California, South Carolina, New York, Massachusetts, and Pennsylvania. Iowa has the most cases, 12, followed by Michigan with 7 and New York with 6.
Jul 3 CDC investigation notice
Department of Defense grant to fund development of new antibiotic class
Originally published by CIDRAP News Jul 3
Canadian biopharmaceutical company Appili Therapeutics announced yesterday that it has received a $3 million grant from the US Department of Defense to develop a novel antibiotic class that targets multidrug-resistant gram-negative bacteria.
Appili, of Halifax, Nova Scotia, will use the money to advance the ATI-1503 antibiotic program, a new class of antibiotics that has shown the potential to address several gram-negative bacterial species deemed high priority pathogens by the World Health Organization, including Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. ATI-1503 is based on the negamycin scaffold, a naturally occurring compound with intrinsic activity against gram-negative bacteria.
The funding comes through the Peer Reviewed Medical Research Program (PRMRP), which supports military-related scientific and medical research.
"Multi-drug-resistant bacteria continue to spread throughout the world, making them one of the most urgent public health threat we are facing worldwide," Appili Therapeutics CEO Kevin Sullivan said in a company press release. "We believe that the ATI-1503 program has the potential to address several of the most dangerous superbugs for the military and civilians alike, and we are grateful for PRMRP's continued support of this promising novel antibiotic class."
Jul 2 Appili Therapeutics press release
Poor prognosis associated with carbapenem-resistant Klebsiella UTIs
Originally published by CIDRAP News Jul 3
New data indicate that UTIs caused by KPC carbapenemase-producing K pneumoniae (KPC-Kp) are associated with higher clinical failure that may be due to inappropriate antibiotic treatment, Spanish investigators reported yesterday in The Journal of Infection.
The retrospective cohort study looked at all patients hospitalized with a UTI caused by K pneumoniae at a university hospital in Cordoba, Spain, from December 2012 through October 2015, a period that saw a hospital outbreak and subsequent endemicity of KPC-Kp. The researchers wanted to assess the impact of UTIs caused by KPC-Kp on clinical failure at day 21 and on 30-day all-cause mortality.
Of the 142 UTI cases included in the analysis, 46 (34.2%) were caused by KPC-Kp and 96 (67.6%) were caused by non–KPC-Kp strains. Clinical failure was more frequent in the KPC-Kp group (41.3% vs 15.6%, P = .001), and, in a non-adjusted analysis, KPC-Kp cause and inappropriate empirical antibiotic therapy were associated with clinical failure at day 21. When both were analyzed in separate models, inappropriate empirical therapy (OR, 2.51; 95% CI, 1.03 to 6.12, P = .04) and KPC-Kp (OR, 2.73; 95% CI, 1.03 to 7.22, P = .04) were both associated with clinical failure.
All-cause mortality (39.1% vs 15.6%, P = .002) and bacteremia (23.9% vs 10.4%, P = .034) were also higher in the KPC-Kp group, but the association was not confirmed in the separate analysis.
The authors of the study conclude, "Our study provides some insights about the association between KPC-Kp aetiology and clinical failure, as well as the implications of inappropriate empirical treatment. It is necessary to insist on the need to initiate appropriate early treatment using, whenever possible, an objective algorithm that helps to indicate empirical antibiotic coverage of KPC-Kp."
Jul 2 J Infect abstract
Study describes how pandemic, multidrug-resistant E coli clone emerged
Originally published by CIDRAP News Jul 2
A study yesterday in the Proceedings of the National Academy of Sciences describes the unique emergence of the pandemic multidrug-resistant E coli clone ST1193.
In the study, scientists from the University of Washington discovered that ST1193 did not acquire high-level resistance to fluoroquinolones through the well-established evolutionary pathway of gradual, stepwise acquisition of mutations in the quinolone resistance-determining regions (QRDRs) of the GyrA and ParC proteins. Instead, they found that the three mutations in the proteins occurred all at once, as part of 11 simultaneous homologous DNA recombination events involving two phylogenetically distant strains of E coli—the uropathogenic clonal complex ST14 and the fluoroquinolone resistant ST10. Further analysis indicates this transfer may have occurred as recently as 12 years ago.
"To our knowledge, such a phenomenon has not been described either in nature or experimentally and shows the power of chromosomal core gene transfer and exchange for adaptive evolution," the authors of the study write.
They add that the findings are important for understanding how successful antibiotic-resistant bacterial strains emerge under the selective pressure created by antibiotic overuse, and suggest that the transfer of large segments of chromosomal DNA may be widespread and represent a significant mechanism of bacterial adaptation.
A July 2018 study in Clinical Infectious Diseases, conducted by some of the same scientists as the current study, found that ST1193—which has also shown resistance to trimethoprim-sulfamethoxazole and tetracycline—accounted for nearly a quarter of the 1,300 fluoroquinolone-resistant E coli isolates collected from nine US hospitals in 2016-17, making it the second-most prevalent clonal group identified. The study also found that ST1193 appears to target younger patients than ST131 H30, the most prevalent E coli clonal group identified among the isolates.
Jul 1 Proc Natl Acad Sci study
Jul 26, 2018, CIDRAP News scan