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1.
Int J Infect Dis ; 122: 313-320, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1882082

ABSTRACT

OBJECTIVES: Although extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) are a global challenge, data on these organisms in low- and middle-income countries are limited. In this study, we sought to characterize colonization data critical for greater antibiotic resistance surveillance efforts. METHODS: This study was conducted in three hospitals and six clinics in Botswana. We conducted ongoing surveillance of adult patients in hospitals and clinics and adults and children in the community. All participants underwent rectal swab sampling to identify ESCrE and CRE. RESULTS: Enrollment occurred from January 15, 2020, to September 4, 2020, but paused from April 2, 2020, to May 21, 2020, because of a countrywide COVID-19 lockdown. Of 5088 individuals approached, 2469 (49%) participated. ESCrE colonization prevalence was 30.7% overall (43% for hospital participants, 31% for clinic participants, 24% for adult community participants, and 26% for child community participants) (P <0.001). A total of 42 (1.7%) participants were colonized with CRE. CRE colonization prevalence was 1.7% overall (6.8% for hospital participants, 0.7% for clinic participants, 0.2% for adult community participants, and 0.5% for child community participants) (P <0.001). ESCrE and CRE prevalence varied substantially across regions and was significantly higher prelockdown versus postlockdown. CONCLUSIONS: ESCrE colonization was high in all settings in Botswana. CRE prevalence in hospitals was also considerable. Colonization prevalence varied by region and clinical setting and decreased after a countrywide lockdown.


Subject(s)
COVID-19 , Enterobacteriaceae Infections , Adult , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Botswana/epidemiology , Carbapenems/pharmacology , Carbapenems/therapeutic use , Cephalosporins , Child , Communicable Disease Control , Delivery of Health Care , Drug Resistance, Microbial , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Hospitals , Humans
2.
mBio ; : e0378821, 2022 Feb 08.
Article in English | MEDLINE | ID: covidwho-1673352

ABSTRACT

The severe acute respiratory coronavirus-2 (SARS-CoV-2) is the cause of the global outbreak of COVID-19. Evidence suggests that the virus is evolving to allow efficient spread through the human population, including vaccinated individuals. Here, we report a study of viral variants from surveillance of the Delaware Valley, including the city of Philadelphia, and variants infecting vaccinated subjects. We sequenced and analyzed complete viral genomes from 2621 surveillance samples from March 2020 to September 2021 and compared them to genome sequences from 159 vaccine breakthroughs. In the early spring of 2020, all detected variants were of the B.1 and closely related lineages. A mixture of lineages followed, notably including B.1.243 followed by B.1.1.7 (alpha), with other lineages present at lower levels. Later isolations were dominated by B.1.617.2 (delta) and other delta lineages; delta was the exclusive variant present by the last time sampled. To investigate whether any variants appeared preferentially in vaccine breakthroughs, we devised a model based on Bayesian autoregressive moving average logistic multinomial regression to allow rigorous comparison. This revealed that B.1.617.2 (delta) showed 3-fold enrichment in vaccine breakthrough cases (odds ratio of 3; 95% credible interval 0.89-11). Viral point substitutions could also be associated with vaccine breakthroughs, notably the N501Y substitution found in the alpha, beta and gamma variants (odds ratio 2.04; 95% credible interval of1.25-3.18). This study thus overviews viral evolution and vaccine breakthroughs in the Delaware Valley and introduces a rigorous statistical approach to interrogating enrichment of breakthrough variants against a changing background. IMPORTANCE SARS-CoV-2 vaccination is highly effective at reducing viral infection, hospitalization and death. However, vaccine breakthrough infections have been widely observed, raising the question of whether particular viral variants or viral mutations are associated with breakthrough. Here, we report analysis of 2621 surveillance isolates from people diagnosed with COVID-19 in the Delaware Valley in southeastern Pennsylvania, allowing rigorous comparison to 159 vaccine breakthrough case specimens. Our best estimate is a 3-fold enrichment for some lineages of delta among breakthroughs, and enrichment of a notable spike substitution, N501Y. We introduce statistical methods that should be widely useful for evaluating vaccine breakthroughs and other viral phenotypes.

4.
Open forum infectious diseases ; 8(Suppl 1):S464-S465, 2021.
Article in English | EuropePMC | ID: covidwho-1564479

ABSTRACT

Background Although CRE are a global threat, data in low- and middle-income countries are scarce. Colonization data are vital for informing antibiotic resistance strategies. We characterized the colonization prevalence of CRE in various settings in Botswana. Methods This study was conducted in 3 districts in Botswana (1 hospital and 2 clinics per district). Adult inpatients and clinic patients were randomly selected for enrollment. Community subjects were enrolled by inviting each enrolled clinic subject to refer up to 3 adults. Each adult clinic or community subject was also asked to refer their children. All subjects had rectal swabs obtained and inoculated on selective chromogenic media for preliminary identification of CRE. Final identification and susceptibility testing were performed using MALDI-TOF MS and VITEK-2, respectively. CRE underwent genotyping for carbapenemase genes. Results Subjects were enrolled from 1/15/20-9/4/20 with a pause from 4/2/20-5/21/20 due to a countrywide COVID lockdown. Of 5,088 subjects approached, 2,469 (49%) participated. Enrollment by subject type was: hospital – 469 (19%);clinic – 959 (39%);community adult – 477 (19%);and community child – 564 (23%). Of 2,469 subjects, the median (interquartile range) age was 32 years (19-44) and 1,783 (72%) were female. 42 (1.7%) subjects were colonized with at least one CRE;10 subjects were colonized with multiple strains. E. coli (n=17), K. pneumoniae (n=20), and E. cloacae complex (n=11) were most common. CRE colonization prevalence was 6.8% for hospital subjects, 0.7% for clinic subjects, 0.2% for adult community subjects, and 0.5% for child community subjects (p< 0.001)). CRE prevalence varied across regions (Figure 1) and was significantly higher pre- vs post-lockdown (Figure 2). VIM and NDM were the most common carbapenemase genes (Figure 3). Figure 1. CRE Colonization - Study Sites Figure 2. CRE Colonization - Temporal Trends FIgure 3. CRE Genotypic Analyses Conclusion CRE colonization was significantly higher in hospital vs community settings in Botswana. CRE prevalence varied by region and decreased significantly following a countrywide lockdown. With CRE prevalence still modest, elucidating risk factors for CRE colonization holds promise in developing strategies to curb further emergence of CRE. Additional investigation of the CRE isolates without identified resistance genes is warranted. Disclosures Robert Gross, MD, MSCE, Pfizer (Other Financial or Material Support, Serve on DSMB for drug unrelated to HIV) Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))

5.
Open forum infectious diseases ; 8(Suppl 1):S243-S243, 2021.
Article in English | EuropePMC | ID: covidwho-1563928

ABSTRACT

Background Although SARS-CoV-2 predominantly targets the respiratory system, it has also been associated with vascular complications including stroke. Identifying COVID-19 patients at elevated risk for stroke can help inform target anticoagulation strategies. We sought to understand how symptoms and laboratory markers at presentation with COVID-19 relate to stroke risk. Methods We enrolled a cohort of 1324 subjects who were hospitalized with COVID-19 across six PennMedicine hospitals between April and August 2020 and performed retrospective, manual chart review to measure exposures including presenting symptoms and admission inflammatory markers. Data were organized with a REDCap database, and analyses were performed using R statistical software, with Bayesian binomial regression models fit using Stan Hamiltonian Monte Carlo via the “brms” package. Results Among 1324 subjects, 19 stroke events were observed within 30 days of COVID-19 diagnosis. Admission inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, and D-dimer, were poor predictors of stroke risk. Among presenting symptoms, including respiratory, gastrointestinal, dermatologic, and neurologic features of COVID-19 disease, only altered mental status documented on presentation (in 529 subjects) was significantly associated with stroke risk (odds ratio 6.06, 95% credible interval 2.16 - 18.7). Conclusion Inflammatory markers associated with COVID-19 disease severity did not discriminate patients at high versus low risk of stroke in this cohort. Altered mental status documented on presentation was significantly associated with incident stroke during COVID-19 disease. Disclosures Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB)) Michael Z. David, MD PhD, GSK (Board Member)

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