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Comparative Genomics and Antimicrobial Resistance Profiling of Elizabethkingia Isolates Reveal Nosocomial Transmission and In Vitro Susceptibility to Fluoroquinolones, Tetracyclines, and Trimethoprim-Sulfamethoxazole.

ABSTRACT: The Elizabethkingia genus has gained global attention in recent years as containing sporadic, worldwide, nosocomial pathogens. Elizabethkingia spp. are intrinsically multidrug resistant, primarily infect immunocompromised individuals, and are associated with high mortality (?20 to 40%). As yet, gaps remain in our understanding of transmission, global strain relatedness, antimicrobial resistance, and effective therapy. Over a 16-year period, 22 clinical and 6 hospital environmental isolates were collected from Queensland, Australia. Identification using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS) and whole-genome sequencing was compared with a global strain data set. Phylogenomic reconstruction robustly identified 22 Elizabethkingia anophelis, 3 Elizabethkingia miricola, 2 Elizabethkingia meningoseptica, and 1 Elizabethkingia bruuniana isolates, most of which branched as unique lineages. Global analysis revealed that some Australian E. anophelis isolates are genetically closely related to strains from the United States, England, and Asia. Comparative genomics of clinical and environmental strains identified evidence of nosocomial transmission in patients, indicating probable infection from a hospital reservoir. Furthermore, broth microdilution against 39 antimicrobials revealed almost ubiquitous resistance to aminoglycosides, carbapenems, cephalosporins, and penicillins. Like other international strains, our isolates expressed susceptibility to minocycline and levofloxacin and the less common trimethoprim-sulfamethoxazole. Our study demonstrates important new insights into the genetic diversity, environmental persistence, and transmission of and potential effective therapy for Australian Elizabethkingia species.

SUBMITTER: Burnard D

PROVIDER: S-EPMC7448627 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Comparative Genomics and Antimicrobial Resistance Profiling of Elizabethkingia Isolates Reveal Nosocomial Transmission and In Vitro Susceptibility to Fluoroquinolones, Tetracyclines, and Trimethoprim-Sulfamethoxazole.

Burnard Delaney D Gore Letitia L Henderson Andrew A Ranasinghe Ama A Bergh Haakon H Cottrell Kyra K Sarovich Derek S DS Price Erin P EP Paterson David L DL Harris Patrick N A PNA

Journal of clinical microbiology 20200824 9

The Elizabethkingia genus has gained global attention in recent years as containing sporadic, worldwide, nosocomial pathogens. Elizabethkingia spp. are intrinsically multidrug resistant, primarily infect immunocompromised individuals, and are associated with high mortality (∼20 to 40%). As yet, gaps remain in our understanding of transmission, global strain relatedness, antimicrobial resistance, and effective therapy. Over a 16-year period, 22 clinical and 6 hospital environmental ...[more]

PMID: 32580952

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Project description:Skin and skin-structure infections are common in ambulatory settings. However, the efficacy of various antibiotic regimens in the era of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is unclear.We enrolled outpatients with uncomplicated skin infections who had cellulitis, abscesses larger than 5 cm in diameter (smaller for younger children), or both. Patients were enrolled at four study sites. All abscesses underwent incision and drainage. Patients were randomly assigned in a 1:1 ratio to receive either clindamycin or trimethoprim-sulfamethoxazole (TMP-SMX) for 10 days. Patients and investigators were unaware of the treatment assignments and microbiologic test results. The primary outcome was clinical cure 7 to 10 days after the end of treatment.A total of 524 patients were enrolled (264 in the clindamycin group and 260 in the TMP-SMX group), including 155 children (29.6%). One hundred sixty patients (30.5%) had an abscess, 280 (53.4%) had cellulitis, and 82 (15.6%) had mixed infection, defined as at least one abscess lesion and one cellulitis lesion. S. aureus was isolated from the lesions of 217 patients (41.4%); the isolates in 167 (77.0%) of these patients were MRSA. The proportion of patients cured was similar in the two treatment groups in the intention-to-treat population (80.3% in the clindamycin group and 77.7% in the TMP-SMX group; difference, -2.6 percentage points; 95% confidence interval [CI], -10.2 to 4.9; P=0.52) and in the populations of patients who could be evaluated (466 patients; 89.5% in the clindamycin group and 88.2% in the TMP-SMX group; difference, -1.2 percentage points; 95% CI, -7.6 to 5.1; P=0.77). Cure rates did not differ significantly between the two treatments in the subgroups of children, adults, and patients with abscess versus cellulitis. The proportion of patients with adverse events was similar in the two groups.We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; ClinicalTrials.gov number, NCT00730028.).

Project description:BackgroundU.S. emergency department visits for cutaneous abscess have increased with the emergence of methicillin-resistant Staphylococcus aureus (MRSA). The role of antibiotics for patients with a drained abscess is unclear.MethodsWe conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim-sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period.ResultsThe median age of the participants was 35 years (range, 14 to 73); 45.3% of the participants had wound cultures that were positive for MRSA. In the modified intention-to-treat population, clinical cure of the abscess occurred in 507 of 630 participants (80.5%) in the trimethoprim-sulfamethoxazole group versus 454 of 617 participants (73.6%) in the placebo group (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). In the per-protocol population, clinical cure occurred in 487 of 524 participants (92.9%) in the trimethoprim-sulfamethoxazole group versus 457 of 533 participants (85.7%) in the placebo group (difference, 7.2 percentage points; 95% CI, 3.2 to 11.2; P<0.001). Trimethoprim-sulfamethoxazole was superior to placebo with respect to most secondary outcomes in the per-protocol population, resulting in lower rates of subsequent surgical drainage procedures (3.4% vs. 8.6%; difference, -5.2 percentage points; 95% CI, -8.2 to -2.2), skin infections at new sites (3.1% vs. 10.3%; difference, -7.2 percentage points; 95% CI, -10.4 to -4.1), and infections in household members (1.7% vs. 4.1%; difference, -2.4 percentage points; 95% CI, -4.6 to -0.2) 7 to 14 days after the treatment period. Trimethoprim-sulfamethoxazole was associated with slightly more gastrointestinal side effects (mostly mild) than placebo. At 7 to 14 days after the treatment period, invasive infections had developed in 2 of 524 participants (0.4%) in the trimethoprim-sulfamethoxazole group and in 2 of 533 participants (0.4%) in the placebo group; at 42 to 56 days after the treatment period, an invasive infection had developed in 1 participant (0.2%) in the trimethoprim-sulfamethoxazole group.ConclusionsIn settings in which MRSA was prevalent, trimethoprim-sulfamethoxazole treatment resulted in a higher cure rate among patients with a drained cutaneous abscess than placebo. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT00729937.).

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Dataset Information

Comparative Genomics and Antimicrobial Resistance Profiling of Elizabethkingia Isolates Reveal Nosocomial Transmission and In Vitro Susceptibility to Fluoroquinolones, Tetracyclines, and Trimethoprim-Sulfamethoxazole.

Publications

Comparative Genomics and Antimicrobial Resistance Profiling of <i>Elizabethkingia</i> Isolates Reveal Nosocomial Transmission and <i>In Vitro</i> Susceptibility to Fluoroquinolones, Tetracyclines, and Trimethoprim-Sulfamethoxazole.

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