Therapeutic Advances in Infectious Disease最新文献

Here we describe a composite vignette of a patient who developed necrotic wounds and systemic infection after reported exposure to xylazine, a veterinary anesthetic found as an adulterant in the unregulated drug supply. While exposure to xylazine-containing compounds via the use of fentanyl is not a new phenomenon, xylazine's prevalence in overdose deaths has escalated, and its geographic distribution has expanded to include rural areas such as Maine. We use this composite vignette to highlight: (1) the growing number of overdoses in Maine where xylazine was found in combination with fentanyl, (2) the potential severe, infection-related complications of xylazine exposure, and (3) describe novel harm reduction strategies that utilize community- and laboratory-based drug checking technology.

Background: Echinocandins are recommended as an initial treatment for invasive candidiasis. Although safety and efficacy profiles of both anidulafungin and caspofungin are well established, direct head-to-head comparisons have not been reported before.

Objective: Compare efficacy and safety of anidulafungin versus caspofungin among patients with invasive candidiasis.

Design: Retrospective observational study.

Methods: Adult patients with invasive candidiasis who were treated with either anidulafungin or caspofungin for ⩾5 days were retrospectively reviewed over a period of 6 years. The primary endpoint was global response, defined as clinical and microbiological success at the end of treatment duration.

Results: A total of 223 patients who received either anidulafungin (n = 176) or caspofungin (n = 47) were initially included. Propensity score matching (based on age, malignancy, level of care, presence of candidemia, and other factors) was performed to improve comparability of the two groups. As a result, 32 patients in the caspofungin arm and 79 patients in the anidulafungin arm were included in the final analysis. Around three-quarters of the cohort had candidemia, and the most common isolated Candida species were C. albicans and C. glabrata. Response rates were comparable between both groups, with the primary outcome of global response showing no significant difference (56.3% for the caspofungin group vs 63.3% for anidulafungin, p = 0.490). Similarly, no differences between the two groups were observed in terms of 90-day all-cause mortality (p = 0.672) or any other secondary endpoints.

Conclusion: Our data suggest that anidulafungin and caspofungin have comparable global response among patients with invasive candidiasis. Additionally, both studied echinocandins showed no significant difference in 90-day all-cause mortality. However, due to the limited sample size, larger studies are needed to confirm these results.

[This corrects the article DOI: 10.1177/20499361241242240.].

Mycoplasma hominis is a rare cause of infective endocarditis, typically reported in immunocompetent patients following valve replacement. We report the first case of post-renal transplant prosthetic valve infective endocarditis and concurrent endophthalmitis caused by M. hominis. A 47-year-old woman with prior aortic valve replacement and renal transplantation presented with fever & atrial fibrillation. She was diagnosed with culture-negative endocarditis complicated by cerebral septic emboli and visual symptoms. Plasma cell-free DNA metagenomic next-generation sequencing identified M. hominis, which was confirmed by culture of aortic abscess tissue. Management included valve replacement surgery and antibiotic therapy with doxycycline and levofloxacin. This case highlights the diagnostic challenges of M. hominis infections, the utility of advanced molecular diagnostics, and the importance of considering M. hominis in immunocompromised patients with culture-negative endocarditis. Donor and recipient screening for M. hominis in recipients with prosthetic heart valves may help prevent infection.

Background: Panton-Valentine Leukocidin (PVL) is one of the major virulence factors known to be associated with invasive, life-threatening Staphylococcus aureus (S. aureus) soft tissue infections. Several studies have shown that methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) are carriers of the lukSF-PV; however, data describing their prevalence and distribution in the Nigerian setting are sparse in the literature, and thus informed the need for the current study.

Objective: We aimed to detect mecA and analysed the risk factors associated with lukSF-PV-producing S. aureus wound infections.

Design: This was a single-centre hospital-based descriptive cross-sectional study conducted between March 2019 and September 2019 at the University of Calabar Teaching Hospital, Calabar, Nigeria.

Methods: Aspirates from participants with soft tissue infections were cultured, and all isolates of S. aureus were tested for the presence of lukSF-PV using endpoint polymerase chain reaction. The mecA was also detected, and antibiotic susceptibility testing was performed.

Results: Eighty S. aureus isolates were identified from 360 participants. Of the eighty, 47 (58.8%) were MRSA and 10 (12.5%) were lukSF-PV-producing S. aureus strains. Of the ten, six were MSSA and four were MRSA, but the difference was not statistically significant. A significant association was observed between lukSF-PV-producing S. aureus-infected wounds and recurrent skin infections (p = 0.024), as well as working in a day care nursery home (p = 0.0008). The majority of S. aureus isolates were susceptible to tigecycline (76%) and vancomycin (76%), followed by susceptibility to linezolid (72.5%), quinupristin/dalfopristin (67.2%), levofloxacin (38.6%) and erythromycin (11.7%).

Conclusion: The prevalence of PVL-positive S. aureus strains causing soft tissue infections in our setting is seemingly high. There is a need for active surveillance of this gene in patients presenting with S. aureus soft tissue infections in our setting, ensure antibiotic susceptibility testing, evaluate the impact of these strains on clinical outcomes and prevent the spread of lukSF-PV-positive S. aureus strains.

Uncomplicated urinary tract infections (uUTIs/acute cystitis) carry a substantial physical and psychological burden that negatively impacts patient quality-of-life, particularly for those who experience recurrent infection. A disconnect can exist between patients and healthcare professionals (HCPs), leading to poor patient-HCP communication, suboptimal treatment, and feelings of frustration and anxiety for many patients. The views of four patient authors with recurrent UTI or chronic uUTI and two HCP authors managing patients with this disease are presented in this Patient Perspectives article. While HCPs recognize both the physical and mental impacts of recurrent uUTIs, most HCPs focus on relieving a patient's physical symptoms, often resulting in the psychological impact being overlooked. Inadequate testing, lengthy diagnostic procedures, and treatment failure caused by antimicrobial resistance (AMR) further exacerbate the problems associated with uUTIs, limiting the effectiveness of treatment options for patients. Enhancing education for patients and HCPs on AMR and the reasons why treatment failure might occur could improve the discourse between HCPs and patients, leading to improvements in the overall patient experience.

Bacterial infections are a major public health threat, with a substantial global burden of ∼5 million deaths in 2019, of which ∼1.27 million were attributed to antibiotic resistance. The formation of bacterial biofilms has significantly enhanced bacterial resistance to antibiotics. Worse still, it increases overall bacterial pathogenesis, contributing to inflammation and potentially to carcinogenesis in humans. Biofilm is implicated in approximately 65% of all bacterial infections and 78.2% chronic wound infections. Alarmingly, about 100-1000-fold increase in antibiotic concentration is required to eradicate bacteria within biofilms, further compromising the health of already ill-patients. Therefore, it is imperative to explore potential antibiofilm agents, especially ones with novel mechanisms of action, to clinically manage inpatient biofilms. Bacteriophage (phage) use is a promising evolutionary approach but is also challenged with potential resistance. Bacteria have developed several antiphage defense mechanisms, some of which exhibit synergistic antiphage activity. In this review, we provide several lines of evidence supporting the efficacy of phages against antibiotic-resistant clinical biofilm-forming bacteria. Observations reveal that phage enzymes disrupt biofilm structural components (e.g., EPS, pectate, and hyaluronic acid) and pave the way for phage infection of naked bacterial cells. We further provide insights into the recent advancements in phage use against biofilm-associated antibiotic-resistant bacteria in patients. Current knowledge shows that phages are rapidly evolving and counteracting antiphage bacterial mechanisms. Here, future perspectives to enhance phages efficacy against biofilm resistance are provided to establish their clinical antibiofilm application. Enhancing the clinical application of phages against biofilms requires addressing bacterial host biofilm resistance and optimizing strategies accordingly. Beyond phage cocktail and phage genetic engineering, conjugating phages with antimicrobial agents (eg., antimicrobial peptides) offers a compelling strategy to enhance phage antibiofilm efficacy.

Background: Manipur, a north-eastern state of India, has a high incidence of intravenous drug use with an equally high prevalence of Hepatitis C virus (HCV) infection.

Objectives: This cross-sectional study aimed to evaluate the impact of certain risk factors enhancing the susceptibility of acquiring HCV.

Design: A total of 1008 participants from various risk groups, from nine districts across the state, were enrolled. Blood samples along with demographic data were collected from the study participants.

Methods: HCV RNA was isolated and nested RT-PCR was performed followed by Sanger sequencing for genotyping. Phylogenetic and phylogeographic studies were further conducted.

Results: Of the total, 493 (48.90%) samples were HCV sero-reactive. Among the sero-reactive samples, 406 (82.35%) were HCV RNA positive. In case of the subgroup PWID + HIV, sero-reactivity (82.22%) and viremia (90.54%) were observed to be exceptionally high. It was noted that HCV sero-reactivity increased four times in people living with HIV (PLHIV) who continued to inject drugs. Three HCV genotypes and eight subtypes were circulating in this study population.

Conclusion: In PLHIV who continued to inject drugs, HCV sero-reactivity increased four-fold. About 40% of the population living with HCV belonged to genotype 6, while genotype 1 showed a noticeable decline. Phylogeographic analyses and spatiotemporal reconstructions revealed that most of the subtypes migrated from far south-east Asian countries like Thailand, Malaysia, Myanmar, and Singapore.

Background: Infective endocarditis (IE) has increased markedly among people who inject drugs (PWID). Harm reduction is a tool to help PWID improve health outcomes and mitigate IE.

Objectives: To understand the knowledge, perceptions, past engagement, and planned use of harm reduction services from syringe services programs (SSPs) for PWID hospitalized with IE.

Design: Qualitative study of PWID hospitalized with IE.

Methods: The research team conducted semi-structured interviews with 16 participants at a large academic hospital from June 2021 to May 2022. Two study personnel coded the interviews and analyzed the data using a combination of structural codes, applied thematic analysis, and thematic comparison.

Results: The majority of participants reported past experiences obtaining safe injection supplies from SSPs, and participants generally viewed SSPs as places for facilitating safer injecting practices, receiving sterile supplies, learning about harm reduction, and/or obtaining overdose reversal kits. However, some participants reported being unable to access SSPs because of their rurality, lack of SSP availability, or transportation barriers. In addition, some participants reported a lack of interest in receiving SSP information during hospitalization, believing that it would enable an undesired return to drug use, while others felt that SSP services would not be relevant for them post-hospitalization.

Conclusion: Patient past and planned use of harm reduction services offered by SSPs was impacted by geographic barriers to accessibility and patient concerns that SSPs would facilitate an undesired return to drug use. Health systems have an opportunity to improve patient usage of harm reduction services post-hospitalization by improving patient education and integrating harm reduction services as tools of care.