Therapeutic Advances in Infectious Disease最新文献

[This corrects the article DOI: 10.1177/20499361241298857.].

Background: Urinary tract infection (UTI) is one of the most common bacterial infections in clinical practice. Given the rapid increase in antimicrobial resistance and the scarcity of new antibiotics, along with the absence of individual antibiogram testing in some countries, there is an urgent need for robust surveillance systems.

Objective: This study aimed to provide evidence for the surveillance of resistance, a crucial component in developing national UTI treatment guidelines and guiding empirical therapy decisions.

Design: This study utilized a retrospective, serial cross-sectional design.

Methods: Antimicrobial surveillance was conducted using data collected from January 1, 2017 to December 31, 2021. A total of 2595 patients with UTIs were recruited for this study. From these patients, 2004 bacterial isolates were identified and subjected to epidemiological and antibiotic resistance analyses.

Results: Escherichia coli (E. coli, 42.7%), Pseudomonas aeruginosa (P. aeruginosa, 11.9%), and Klebsiella pneumoniae (K. pneumoniae, 10.9%) were identified as the predominant causes of UTIs. E. coli isolates demonstrated a high level of sensitivity (80%-90%) to carbapenems (imipenem, ertapenem, and meropenem), aminoglycosides (amikacin), piperacillin/tazobactam, cefoperazone/sulbactam, and fosfomycin. The antibiotic resistance rates of K. pneumoniae strains consistently exceeded 50%, except for amikacin, ertapenem, imipenem, meropenem, and fosfomycin. Notably, all K. pneumoniae strains isolated from patients with UTIs were resistant to ampicillin. During the coronavirus disease pandemic, the E. coli and K. pneumoniae isolates exhibited reduced antibiotic resistance compared to the pre-pandemic period. The resistance rate of P. aeruginosa isolates remained consistently high (60%-70%).

Conclusion: Amikacin, ertapenem, imipenem, meropenem, and fosfomycin are promising treatment options for enterobacterial UTIs. However, their efficacy against P. aeruginosa is limited. This study revealed alarmingly high rates of primary etiological pathogen resistance to commonly prescribed empirical therapies for UTIs. These findings provide crucial data for optimizing national guidelines and implementing personalized treatment strategies to enhance the effectiveness of UTI treatments.

Background: In addition to structural interventions such as syringe services and naloxone distribution, harm reduction (HR) is also a relational approach to care encompassing principles such as patient autonomy and pragmatism that can be implemented in healthcare teams to improve outcomes for people with HIV (PWH) who use drugs. Evidence suggests that using a relational HR framework to operationalize care for PWH who use drugs may improve the patient-provider relationship, thus positively impacting HIV outcomes. We previously found that negative attitudes toward people who use drugs are negatively associated with acceptance of HR; however, little is known about how HIV providers conceptualize the patient-provider relationship with PWH who use drugs.

Objectives: The aim of this study was to describe the ways healthcare workers (HCWs) characterize interactions with PWH who use drugs and if these characterizations reflect relational HR or missed opportunities to improve the patient-provider relationship.

Design: We used a qualitative descriptive design to characterize HCWs' descriptions of their interactions with PWH who use drugs.

Methods: We interviewed providers (n = 23) working at three HIV clinics in the United States to assess their interactions with patients. Providers included anyone who had worked at their respective clinic for ⩾1 year and who had face-to-face contact with patients (e.g., front desk staff, nurses, physicians, and social workers). Data were coded thematically via Dedoose.

Results: We discovered that HCWs characterize positive patient-provider interactions that both reflect HR principles and may not align with the principles of HR. Examples include when patients appear comfortable with and trusting of their provider, when patients feel heard by their provider, and when providers feel they are responsive to patient needs. However, other HCWs described positive interactions as counter to relational HR.

Conclusion: HCW descriptions of positive interactions in line with relational HR in their conceptualization of patient-provider interactions with PWH who use drugs have the potential to guide efforts in increasing the acceptability of HR in HIV care. Given evidence showing HR improves outcomes for those who use substances, findings suggest missed opportunities to incorporate relational HR into the patient-provider relationship in HIV primary care settings.

Registration: NCT05404750.

Background: At present, there is a need for more substantial real-world evidence on the factors influencing the effectiveness of tuberculosis (TB) treatment in HIV/TB co-infected patients.

Objectives: This retrospective study aims to identify factors affecting TB treatment effectiveness in HIV/TB co-infected patients.

Design: Retrospective cross-sectional study.

Methods: We included 461 HIV/TB co-infected patients, deriving 742 samples based on each initial positive TB test period. A total of 7788 valid treatment records corresponding to 17 TB drug compositions and 150 clinical indicators (each > 100 records) were used for analysis. Data mining techniques were employed, including consensus clustering, Fisher's exact test, stratified analysis, multivariate logistic regression analysis, and three modeling approaches (logistic regression, support vector machine, and random forest).

Results: The TB treatment effectiveness of CD4⁺ T cell count ⩽ 42 is significantly lower than that of the sample group > 42 (aOR: 1.77, 95% CI: 1.15-2.74, p = 0.010). The TB treatment effectiveness of the "rifabutin and levofloxacin alone or in combination" group is significantly higher than that of the "other first- and second-line anti-TB drugs in combination" group (aOR: 0.10, 95% CI: 0.01-0.64, p = 0.022). Significant differences exist in factors between TB treatment effective and ineffective groups, including age (aOR: 2.12, 95% CI: 1.10-4.20, p = 0.027), pre-treatment high-density lipoprotein (HDL) cholesterol (aOR: 0.47, 95% CI: 0.25-0.89, p = 0.022), pre-treatment CD8⁺ T cell count (aOR: 0.55, 95% CI: 0.33-0.90, p = 0.019), pre-treatment neutrophil percentage (aOR: 0.68, 95% CI: 0.48-0.96, p = 0.030), rifabutin (aOR: 1.59, 95% CI: 1.09-2.32, p = 0.016), and cycloserine (aOR: 0.21, 95% CI: 0.03-0.77, p = 0.041). The best area under the receiver operating characteristic curve of the test set under three modeling methods is 0.560-0.763. Rate of lymphocyte percentage recovering to normal is significantly higher in the TB treatment-effective group than in the treatment-ineffective group (aOR: 1.83, 95% CI: 1.09-3.10, p = 0.022).

Conclusion: CD4⁺ T cell count of 42/μL assists TB treatment effectiveness evaluation. Rifabutin and levofloxacin show more therapeutic benefits. Lymphocyte percentage can serve as an effective TB therapeutic and diagnostic target. Age, pre-treatment factors (HDL cholesterol, CD8⁺ T cell count, and neutrophil percentage), rifabutin, and cycloserine are significantly associated with TB treatment effectiveness. Factors affecting TB treatment effectiveness for HIV/TB co-infected patients need more evidence.

Both acute traveler's diarrhea and sexually transmitted infections are common causes of fever in the returned traveler, with the male sex corresponding to two-fold increased odds of a sexually transmitted infection (STI) diagnosis related to travel. Shigella flexneri is the most common cause of shigellosis in low- and middle-income countries, while within the men who have sex with men (MSM) population, outbreaks of S. flexneri 3a, S. flexneri 2a, and S. sonnei have been reported. We herein present a case of a febrile returned MSM traveler with a predominantly gastrointestinal presentation and proctocolitis whose microbiological work-up confirmed coinfection with S. flexneri and rectal gonorrhea. Based on his travel history and epidemiologic risk factors, it is unclear if food- and waterborne shigellosis versus transmission via sexual contact was the major route of acquisition. This case highlights the broad differential for proctocolitis and the importance of consideration of intercurrent infections.

Background: Immunocompromised adults may experience severe COVID-19 outcomes, necessitating a multifaceted treatment approach. Studies from the Delta period showed benefit from monoclonal antibody (mAb) therapy that was most pronounced among anti-spike IgG seronegative individuals. With widespread vaccination and shifting SARS-CoV-2 variants in the Omicron period, clinical predictors of anti-spike IgG seronegativity, and impacts on clinical outcomes, remain incompletely characterized.

Objectives: We describe outcomes from a cohort of immunocompromised adults with COVID-19 stratified by anti-spike IgG serostatus and receipt of mAb therapy during the Omicron period to evaluate clinical impact.

Design: This was a retrospective study of immunocompromised adults with mild-moderate COVID-19 presenting between December 2021 and October 2022.

Methods: Charts were reviewed to assess anti-spike IgG serostatus, receipt of mAb therapy, and 28-day outcomes including conventional oxygen use, high-flow oxygen use, mechanical ventilation, and death.

Results: A total of 276 individuals were included, of whom 252 (91%) were partially or fully vaccinated, 190 (69%) were anti-spike IgG seropositive, and 225 (82%) received mAb therapy. A majority were solid organ transplant recipients (169, 61%), with anti-spike IgG seronegatively significantly associated with mycophenolate-based immunosuppression or comorbid chronic kidney disease. Conventional oxygen use among seropositive patients receiving mAb, seronegative patients receiving mAb, seropositive patients not receiving mAb, and seronegative patients not receiving mAb were 2/154 (1%), 5/71 (7%), 6/36 (17%), and 4/15 (27%), respectively. Across the cohort, high-flow oxygen use, mechanical ventilation, and death occurred in 6 (2%), 4 (3%), and 3 (1%) individuals, respectively.

Conclusion: Clinical outcomes in a predominantly vaccinated, immunocompromised cohort with mild-moderate COVID-19 during the Omicron period appeared to vary with anti-spike IgG serostatus and receipt of mAb therapy. Observed trends would benefit from prospective studies during future iterations of COVID-19 therapeutics to inform treatment decisions for immunocompromised adults.

Background: The proliferation of Plasmodium parasites resistant to antimalarial drugs poses a serious threat to human life and remains an obstacle to managing and eradicating Plasmodium falciparum. The surveillance of molecular markers has become necessary to monitor the spread of resistant haplotypes and discover emerging mutations.

Objective: This molecular epidemiological study aimed to evaluate the prevalence of known mutations in the drug resistance genes Pfcrt, Pfmdr1, Pfdhfr and Pfdhps in the Central Region of Ghana.

Design: A multi-centre cross-sectional study.

Methods: This prospective study utilised dried blood spots from individuals with P. falciparum-infection from five districts in the Central Region of Ghana. Selective Whole Genome Amplification (sWGA) and Single Nucleotide Polymorphisms (SNPs) in P. falciparum chloroquine transporter genes (Pfcrt), P. falciparum multidrug resistance 1 (Pfmdr1), P. falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) were analysed.

Results: Whole genome sequencing was carried out on 522 samples. Of these, 409 (78%) samples were successfully sequenced. Six (6) of the sequenced samples were of co-infection of other parasite species with P. falciparum and excluded from the analysis. Analysis of the Pfcrt gene revealed 0.5% were CVIET (C72, V73, M74I, N75E, K76T) while the Pfcrt CVMNK (C72, V73, M74, N75, K76) wild-type haplotypes were 97% with (2.5%) (CV[M/I][N/E][K/T]) being mixed haplotypes. In the Pfmdr1 gene, monoclonal haplotypes; NFD (N86, Y184F, D1246) and YFN (N86Y, Y184F, D1246N) occurred at 44% and 9.8%, respectively, whereas mixed- haplotypes (N[Y/F]D and [N/Y][Y/F]D) were 23.5% and 0.3%, respectively. Combined Pfdhfr/Pfdhps genes yielded about 88% Pfdhfr IRNI (N51I, C59R, S108N, I164) + Pfdhps A437G haplotypes (conferring partial resistance to Sulphadoxine-Pyrimethamine (SP)) while 9% of the parasites had Pfhdfr IRNI + Pfdhps A437G + K540E haplotypes (conferring full resistance to SP). The wild-type haplotype, Pfdhfr (N51, C59, S108, I164) and Pfdhps (S436, A437, K540, A581, A613) was not observed.

Conclusion: The findings show a low prevalence of CVIET and relatively higher rates for Pfmdr1 NFD and parasites with Pfdhfr IRNI (N51I, C59R, S108N, I164) + Pfdhps A437G haplotypes. These observations advocate for enhanced surveillance which is inimical to malaria management in an endemic area.

Background: Tuberculosis (TB) remains a significant global health challenge, especially among people living with HIV. Drug-resistant TB (DR-TB) complicates treatment outcomes in high-burden countries like Uganda, particularly for adolescents and young adults living with HIV (AYALH).

Objectives: We described the characteristics, treatment outcomes, and factors associated with treatment success among AYALH and DR-TB at a TB treatment unit in Mulago National Referral Hospital, Kampala, Uganda.

Design: A retrospective cohort study was conducted.

Methods: Medical records of AYALH treated for DR-TB between January 2013 and December 2021 were reviewed. Descriptive statistics and multivariable logistic regression were used to analyze treatment outcomes and associated factors.

Results: Among 327 participants (mean age: 28.2 years, SD: 4.75; 52.6% male), the treatment success rate was 65.7%. A body mass index (BMI) ⩾ 18.5 kg/m² (adjusted odds ratio [aOR]: 0.53, 95% CI: 0.33-0.83, p = 0.005), Efavirenz-based antiretroviral therapy (ART) regimens (aOR: 0.56, 95% CI: 0.35-0.89, p = 0.014), and primary DR-TB (aOR: 0.42, 95% CI: 0.28-0.64, p < 0.001) were significantly associated with treatment success.

Conclusion: The study revealed a treatment success in only two-thirds of participants emphasizing persistent challenge of achieving optimal treatment outcomes for AYALH. The findings highlight that a higher BMI and Efavirenz-based ART regimens are significantly associated with improved treatment success pointing to the necessity for addressing nutritional needs and optimizing ART regimens to improve the management of DR-TB among AYALH.

Anthropogenic climate change, primarily driven by greenhouse gas emissions, is reshaping ecosystems and creating conditions that affect 58% of all known human infectious diseases, including fungal infections. Specifically, increasing temperatures, changing precipitation patterns, and extreme weather events are influencing fungal growth, distribution, and virulence. These factors may expand the geographic range of pathogenic fungi, exposing populations to novel, potentially more virulent, or drug-resistant strains. Simultaneously, human factors such as declining immunity, aging populations, and increased use of immunosuppressive therapies are enhancing host susceptibility. This review explores the intricate relationship between climate change and fungal infections, highlighting pathogens that may demonstrate increased virulence and antifungal resistance, along with emerging novel pathogens. The clinical implications are profound, with increased morbidity, mortality, and the spread of fungal infections into new regions. Immediate action is required to develop policies, educational initiatives, and novel antifungal therapies, enhance early diagnostic capabilities, and address healthcare disparities to mitigate the growing burden of fungal infections.

Background: Nurse-driven protocols (NDPs) for urinary catheter removal are proven tools for decreasing catheter-associated urinary tract infections (CAUTIs); however, they are not used consistently in acute care settings.

Objective: To determine the impact of a NDP for urinary catheter removal on CAUTI rates and device utilization ratio.

Design: Pre/postintervention, observational study at a 160-bed, level 1a academically affiliated Veterans Affairs (VA) hospital.

Methods: CAUTI rates and device utilization ratios were examined before and after implementation of the NDP.

Results: The CAUTI rate decreased from 0.99 per 1,000 urinary catheter days in the preintervention period to 0.27 per 1000 urinary catheter days in the postintervention period. The device utilization ratio (catheter days/patient days) decreased from 14% in the preintervention period to 12% in the postintervention period.

Conclusion: The NDP reduced the CAUTI rate and the device utilization ratio. A multidisciplinary project team and use of a data visualization dashboard may be valuable implementation strategies to increase utilization of NDPs such as HOUDINI.