Purpose
Annual screening for asymptomatic infections with
Chlamydia trachomatis
(CT) and
Neisseria gonorrhoeae
(NG) is recommended by international guidelines in people living with HIV but uptake in ...routine care remains poor. This study analyzed the effects of the implementation of a CT/NG screening program in a primary HIV treatment center.
Methods
In this single-center cohort study, we included men having sex with men (MSM) living with HIV during the study period from January 2016 to December 2019. From January 2018 on, annual sexual health counseling including CT/NG screening was proactively offered to all MSM presenting at the center. CT/NG screening rates, test positivity rates and case detection rates in the years 2018 and 2019 were compared to those in the years 2016 and 2017.
Results
A total of 234 patients were enrolled in the study contributing to 798.7 patient years (py) during the four-year study period. Screening rates increased from 3.1% and 3.9% in 2016 and 2017 to 51.1% in 2018 and decrease to 35.4% in 2019. Over the study period, 19.7% (46/234) had at least one positive CT/NG result. After the intervention, case detection per 100 py increased for CT (2016: 2.6, 2017: 3.7, 2018: 7.7, 2019: 7.1) and NG (2016: 3.2, 2017: 3.1, 2018: 5.3, 2019: 7.6). The number needed to test was 8.9 for CT and 10.4 for NG.
Conclusion
Regular CT/NG screening is feasible in a primary care setting, leads to an increase in case detection and may contribute to decrease transmission and complications of CT/NG.
Trial registration
The trial is registered in ClinicalTrials.gov (NCT02149004).
Arboviral diseases remain a significant health concern worldwide, with over half the world's population at risk for dengue alone. Without a vaccine or targeted treatment, the most effective strategy ...of prevention is vector management with community involvement. mHealth interventions, like WhatsApp, offer promising results for engaging communities and promoting healthier behaviors. This study explores the feasibility of integrating WhatsApp in vector control activities to improve arbovirus prevention in Colombia. A mixed-methods approach was employed to assess the WhatsApp-based intervention. WhatsApp messages were sent to 45 community women for 5 weeks to increase their knowledge and practices about dengue, Zika, and chikungunya. Pre-and-post surveys and focus group discussions were conducted in community settings to measure the feasibility and acceptability of this intervention. Chat reviews were done to assess the usability of users. A total of 1566 messages were exchanged in 45 WhatsApp chats. High acceptance and good usability (82% of users used the app for replying) were reported in this study. WhatsApp messages were perceived as short, clear, and enjoyable. Users liked the frequency, and design of messages. Pre- and post-surveys demonstrated improvements in the knowledge and practices of arboviral diseases. The intention to apply this knowledge in practice was reflected in a significant improvement, particularly in cleaning the laundry tank once a week (pre 62.1% to post 89.6%,
< 0.008). This study suggests that using WhatsApp as an additional tool could be a feasible, acceptable, and affordable strategy for improving the adoption of better practices in the prevention of arboviral diseases.
Multidrug resistance poses global challenges, particularly with regard to Gram-negative bacterial infections. In view of the lack of new antibiotics, drug enhancers, such as efflux pump inhibitors ...(EPIs), have increasingly come into focus. A number of chemically diverse agents have been reported to inhibit AcrB, the main multidrug transporter in
, and homologs in other Gram-negative bacteria. However, due to the often varying methodologies used for their characterization, results remain difficult to compare. In this study, using a defined selection of antibiotics known to be efflux substrates, we reevaluated 38 published compounds for their
EPI activity. When examined in an
strain with stable wild-type AcrB overexpression, we found 17 compounds showing at least fourfold enhancing potency with more than 2 out of 10 test drugs (belonging to eight antibiotic classes). Pyranopyridines (MBX series) were confirmed as the most potent inhibitors among agents reported so far. A new and surprising finding was that their activity, unlike that of the pyridylpiperazine EPI BDM88855, was highly susceptible to the AcrB double-mutation G141D_N282Y, which had previously been shown to diminish drug enhancing of 1-(1-naphthylmethyl)piperazine in a predominantly substrate-specific manner. Conversely, transmembrane region mutation V411A, while eliminating the drug potentiating of the BDM compound, did not decrease the activity of the MBX EPIs. Besides comparative reassessment of the potency of reported EPIs, the study demonstrated the usefulness of mutagenesis approaches providing tools for an initial discrimination of EPIs regarding their mode of function.IMPORTANCEInfections with difficult-to-treat multidrug-resistant bacteria pose an urgent global threat in view of the stagnating development of new antimicrobial substances. Efflux pumps in Gram-negative pathogens are known to substantially contribute to multidrug resistance making them promising targets for chemotherapeutic interventions to restore the efficacy of conventional antibiotics. In the present study, the
activity of previously reported efflux pump inhibitors was reassessed using standardized conditions. Relevant drug sensitizing activity could be proven for almost half of the tested compounds. Further characterization of potent inhibitors was achieved by investigating the impact of specific efflux pump mutations. A double-mutation previously known to decrease the activity of the arylpiperazine 1-(1-naphthylmethyl)piperazine also impaired that of the highly efficient pyranopyridine efflux pump inhibitors. Our findings provide direct comparability of reported efflux pump inhibitors and contribute to the elucidation of their mode of action.
Co-trimoxazole (trimethoprim/sulfamethoxazole) is clinically valuable in treating skin and soft tissue infections (SSTIs) caused by community-associated methicillin-resistant Staphylococcus aureus ...(MRSA). The genetic basis of emerging trimethoprim/sulfamethoxazole resistance in S. aureus from Africa is unknown. Such knowledge is essential to anticipate its further spread. We investigated the molecular epidemiology of trimethoprim resistance in S. aureus collected in and imported from Africa.
Five hundred and ninety-eight human S. aureus isolates collected at five locations across sub-Saharan Africa Gabon, Namibia, Nigeria (two) and Tanzania and 47 isolates from travellers treated at six clinics in Europe because of SSTIs on return from Africa were tested for susceptibility to trimethoprim, sulfamethoxazole and trimethoprim/sulfamethoxazole, screened for genes mediating trimethoprim resistance in staphylococci dfrA (dfrS1), dfrB, dfrG and dfrK and assigned to spa genotypes and clonal complexes.
In 313 clinical and 285 colonizing S. aureus from Africa, 54% of isolates were resistant to trimethoprim, 21% to sulfamethoxazole and 19% to trimethoprim/sulfamethoxazole. We found that 94% of trimethoprim resistance was mediated by the dfrG gene. Of the 47 S. aureus isolates from travellers with SSTIs, 27 (57%) were trimethoprim resistant and carried dfrG. Markers of trimethoprim resistance other than dfrG were rare. The presence of dfrG genes in S. aureus was neither geographically nor clonally restricted.
dfrG, previously perceived to be an uncommon cause of trimethoprim resistance in human S. aureus, is widespread in Africa and abundant in imported S. aureus from ill returning travellers. These findings may foreshadow the loss of trimethoprim/sulfamethoxazole for the empirical treatment of SSTIs caused by community-associated MRSA.
Background
Patients with cancer are considered a high‐risk group for viral pneumonia, with an increased probability of fatal outcome. Here, we investigated the clinical characteristics and outcome of ...patients with solid and hematological cancers and concomitant Covid‐19 at a Comprehensive Cancer Center in a Covid‐19 hotspot area in Germany.
Methods
We performed a retrospective single center cohort study of 39 patients with hematological and solid cancers who were hospitalized at the University Hospital Freiburg for Covid‐19. Using univariate and multivariate Cox regression models we compared time to severe events and overall survival to an age‐matched control cohort of 39 patients with confirmed Covid‐19 without a cancer diagnosis.
Results
In the cancer cohort 29 patients had a diagnosis of a solid tumor, and 10 had a hematological malignancy. In total, eight patients (21%) in the cancer and 14 patients (36%) from the noncancer cohort died during the observation period. Presence of a malignancy was not significantly associated with survival or time to occurrence of severe events. Major influences on mortality were high IL‐6 levels at Covid‐19 diagnosis (HR = 6.95, P = .0121) and age ≥ 65 years (HR = 6.22, P = .0156).
Conclusions
Compared to an age‐matched noncancer cohort, we did not observe an association between a cancer diagnosis and a more severe disease course or higher fatality rate in patients with Covid‐19. Patients with a hematological malignancy showed a trend towards a longer duration until clinical improvement and longer hospitalization time compared to patients with a solid cancer. Cancer per se does not seem to be a confounder for dismal outcome in Covid‐19.
In this retrospective single center cohort study at a Comprehensive Cancer Center in Germany we did not observe an association between a cancer diagnosis and a more severe disease course or higher fatality rate in patients with Covid‐19 when compared to an age‐matched control cohort of patients with confirmed Covid‐19 without a cancer diagnosis.
This double-blind, multicenter trial compared the efficacy and safety of a single daily oral dose of moxifloxacin with oral combination therapy in low-risk febrile neutropenic patients with cancer.
...Inclusion criteria were cancer, febrile neutropenia, low risk of complications as predicted by a Multinational Association for Supportive Care in Cancer (MASCC) score > 20, ability to swallow, and ≤ one single intravenous dose of empiric antibiotic therapy before study drug treatment initiation. Early discharge was encouraged when a set of predefined criteria was met. Patients received either moxifloxacin (400 mg once daily) monotherapy or oral ciprofloxacin (750 mg twice daily) plus amoxicillin/clavulanic acid (1,000 mg twice daily). The trial was designed to show equivalence of the two drug regimens in terms of therapy success, defined as defervescence and improvement in clinical status during study drug treatment (< 10% difference).
Among the 333 patients evaluated in an intention-to-treat analysis, therapy success was observed in 80% of the patients administered moxifloxacin and in 82% of the patients administered combination therapy (95% CI for the difference, -10% to 8%, consistent with equivalence). Minor differences in tolerability, safety, and reasons for failure were observed. More than 50% of the patients in the two arms were discharged on protocol therapy, with 5% readmissions among those in either arm. Survival was similar (99%) in both arms.
Monotherapy with once daily oral moxifloxacin is efficacious and safe in low-risk febrile neutropenic patients identified with the help of the MASCC scoring system, discharged early, and observed as outpatients.
Antimicrobial peptides are multifunctional effector molecules of innate immunity. In this study we investigated whether endothelial cells actively contribute to innate defense mechanisms by ...expression of antimicrobial peptides. We therefore stimulated human umbilical vein endothelial cells (HUVEC) with inflammatory cytokines, Th17 cytokines, heat-inactivated bacteria, bacterial conditioned medium (BCM) of Staphylococcus aureus and Streptococcus sanguinis, and lipoteichoic acid (LTA). Stimulation with single cytokines induced discrete expression of human β-defensin 3 (hBD3) by IFN-γ or IL-1β and of ribonuclease 7 (RNase7) by TNF-α without any effects on LL-37 gene expression. Stronger hBD3 and RNase7 induction was observed after combined stimulation with IL-1β, TNF-α and IFN-γ and was confirmed by high hBD3 and RNase7 peptide levels in cell culture supernatants. In contrast, Th17 cytokines or stimulation with LTA did not result in AMP production. Moreover, only BCM of an invasive S. aureus bacteremia isolate induced hBD3 in HUVEC. We conclude that endothelial cells actively contribute to prevent dissemination of pathogens at the blood-tissue-barrier by production of AMPs that exhibit microbicidal and immunomodulatory functions. Further investigations should focus on tissue-specific AMP induction in different endothelial cell types, on pathogen-specific induction patterns and potentially involved pattern-recognition receptors of endothelial cells.
To analyse the rectal carriage rate and the molecular epidemiology of vancomycin-resistant Enterococcus faecium (VREfm) recovered from patients upon hospital admission.
Adult patients were screened ...at six German university hospitals from five different federal states upon hospital admission for rectal colonization with VREfm between 2014 and 2018. Molecular characterization of VREfm was performed by WGS followed by MLST and core-genome MLST analysis.
Of 16350 patients recruited, 263 were colonized with VREfm, with increasing prevalence rates during the 5 year study period (from 0.8% to 2.6%). In total, 78.5% of the VREfm were vanB positive and 20.2% vanA positive, while 1.2% harboured both vanA and vanB. The predominant ST was ST117 (56.7%) followed by ST80 (15%), ST203 (10.9%), ST78 (5.7%) and ST17 (3.2%). ST117/vanB VREfm isolates formed a large cluster of 96 closely related isolates extending across all six study centres and four smaller clusters comprising 13, 5, 4 and 3 isolates each. In contrast, among the other STs inter-regional clonal relatedness was rarely observed.
To our knowledge, this is the largest admission prevalence and molecular epidemiology study of VREfm. These data provide insight into the epidemiology of VREfm at six German university hospitals and demonstrate the remarkable inter-regional clonal expansion of the ST117/vanB VREfm clone.
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