Open Forum Infectious Diseases最新文献

Background: The objective of this study was to identify antibiotic stewardship (AS) opportunities in Latin American medical-surgical intensive care units (MS-ICUs) and general wards (Gral-wards).

Methods: We conducted serial cross-sectional point prevalence surveys in MS-ICUs and Gral-wards in 41 Latin American hospitals between March 2022 and February 2023. Patients >18 years of age in the units of interest were evaluated for antimicrobial use (AU) monthly (MS-ICUs) or quarterly (Gral-wards). Antimicrobial data were collected using a standardized form by the local AS teams and submitted to the coordinating team for analysis.

Results: We evaluated AU in 5780 MS-ICU and 7726 Gral-ward patients. The hospitals' median bed size (interquartile range) was 179 (125-330), and 52% were nonprofit. The aggregate AU prevalence was 53.5% in MS-ICUs and 25.5% in Gral-wards. Most (88%) antimicrobials were prescribed to treat infections, 7% for surgical prophylaxis and 5% for medical prophylaxis. Health care-associated infections led to 63% of MS-ICU and 38% of Gral-ward AU. Carbapenems, piperacillin-tazobactam, intravenous (IV) vancomycin, and ampicillin-sulbactam represented 50% of all AU to treat infections. A minority of IV vancomycin targeted therapy was associated with documented methicillin-resistant Staphylococcus aureus infection or therapeutic drug monitoring. In both units, 17% of antibiotics prescribed as targeted therapy represented de-escalation, while 24% and 15% in MS-ICUs and Gral-wards, respectively, represented an escalation of therapy. In Gral-wards, 32% of antibiotics were used without a microbiologic culture ordered. Half of surgical prophylaxis antibiotics were prescribed after the first 24 hours.

Conclusions: Based on this cohort, areas to improve AU in Latin American hospitals include antibiotic selection, de-escalation, duration of therapy, and dosing strategies.

Background: There are limited and conflicting data regarding the impact of race or ethnicity on the rate of gram-negative antimicrobial resistance. This study was performed to determine whether there is a difference in extended-spectrum beta-lactamase (ESBL) Escherichia coli infection or colonization in minoritized patients when compared to White patients from a diverse US Midwestern city.

Methods: A case control study was performed, with controls with non-ESBL E. coli matched 1:1 to patients with ESBL-producing E coli based on age, sex, and ZIP code. A variety of other evidence-based factors for ESBL Enterobacterales infection and colonization were collected via chart review. Multivariate conditional logistic regression assessed the odds of minoritized patients as compared to White patients, while controlling for other common risk factors for ESBL Enterobacterales.

Results: A total of 364 matched pairs were included in the analysis. Females were the majority of the sample (91%), with median age of 65 years. The majority of the sample identified as White (73%), followed by Hispanic (14%) and Black (10%). Urine cultures made up the majority of the cultures in the sample (97%), and this was similar between ESBL and non-ESBL groups. While controlling for these risk factors for ESBL E coli, minoritized patients had a statistically significant greater odds of ESBL-producing E coli (odds ratio, 2.53; 95% confidence interval, 1.68-3.82).

Conclusions: In our sample, which is demographically similar to the United States, minoritized patients had higher odds of ESBL-producing E coli. Further research on the drivers for this disparity is needed.

We retrospectively reviewed patients with Corynebacterium striatum bacteremia treated with daptomycin. All 11 isolates were initially susceptible to daptomycin, but the emergence of daptomycin nonsusceptibility during treatment and clinical failure occurred in 36% and 45% of patients, respectively.

Background: Among people with HIV (PWH), COVID-19 is common and potentially severe. We leveraged REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) to assess the effects of statin therapy for cardiovascular disease prevention on COVID-19 outcomes (incidence and serious cases) among a global cohort of PWH.

Methods: COVID-19 data collection was implemented April 2020 to capture events from January 2020. COVID-19 was defined by positive test result or clinical diagnosis and serious COVID-19 according to the International Conference on Harmonisation definition. Among participants in follow-up on 1 January 2020, Cox proportional hazards modeling was used to estimate the hazard ratio (HR) of COVID-19 (pitavastatin/placebo), stratified by Global Burden of Disease region. Modification of statin effect following COVID-19 vaccination was evaluated via interaction with time-updated vaccination status.

Results: Among 6905 PWH, 32% were natal female and 41% were Black or African American. The median age was 53 years and the 10-year atherosclerotic cardiovascular disease risk score 4.5%. Statin therapy did not reduce COVID-19 incidence (HR, 1.05; 95% CI, .95-1.15) but appeared to reduce incidence of serious COVID-19 (HR, 0.75; 95% CI, .52-1.09). Among 1701 PWH with COVID-19, the relative risk (pitavastatin/placebo) for serious COVID-19 was 0.73 (95% CI, .52-1.03). The treatment effect size for serious COVID-19 fell within the hypothesized range, but the 95% CI crossed 1 given fewer-than-anticipated cases (117 vs 200). Furthermore, 83% reported COVID-19 vaccination by end of study, with a strong protective effect on serious COVID-19 (HR, 0.27; 95% CI, .14-.53; P < .0001). A protective statin effect was observed prior to vaccination.

Conclusions: Among PWH, statin therapy had no effect on COVID-19 incidence but showed potential to reduce risk of serious COVID-19 prior to COVID-19 vaccination.

Clinical trials registration: NCT02344290 (ClinicalTrials.gov).

Background: Reduced vancomycin (VAN) susceptibility in clinical Clostridioides difficile isolates is correlated with poor clinical outcomes. However, factors associated with infection with these strains are unknown. The goal of this study was to determine risk factors for reduced VAN susceptibility among clinical isolates of C. difficile.

Methods: This multicenter cohort study included adults with C. difficile infection (CDI) between 2016 and 2021. Clinical C. difficile isolates underwent agar dilution VAN susceptibility testing and ribotyping. Reduced susceptibility was defined as a minimum inhibitory concentration (MIC) > 2 µg/mL. Medical charts were reviewed for host, pathogen, and hospital characteristics and assessed for predictors of reduced VAN susceptibility.

Results: Five hundred and ninety-four hospitalized patients with CDI between 2016 and 2021 (female: 57%, age >65 years: 55%, White/non-Hispanic: 59%, nonsevere CDI episode: 53%) were identified. Of 594 isolates, 173 (29%) had reduced VAN susceptibility (MIC₅₀: 2 µg/mL, MIC₉₀: 4 µg/mL). In multivariable analysis, ribotype (RT) 027 (odds ratio [OR]: 13.4; 95% confidence interval [CI], 7.7-23.4; P < .0001) and RT 255 (OR: 2.9; 95% CI, 1.4-6.1; P = .005) were positively associated with reduced VAN susceptibility whereas RT 014-020 (OR: 0.41; 95% CI, 0.21-0.80; P = .0092) was more likely to be susceptible to VAN. The prevalence of strains with reduced VAN susceptibility increased over time (P = .0163). No patient- or hospitalization-specific variable predicted infection with reduced susceptibility strain.

Conclusions: Certain ribotypes, including RT 027, were the sole independent risk factors for reduced VAN susceptibility. Increased clinical surveillance of these strains, especially RT 027, and their antibiotic susceptibly is warranted to inform prescribing practices.

Background: Necrotizing soft tissue infections (NSTIs) are often caused by group A Streptococcus (GAS). As the number of invasive GAS infections decreased during the coronavirus disease 2019 (COVID-19) pandemic restrictions, this study aimed to compare the occurrence of GAS-NSTIs before, during, and after the COVID-19 pandemic restrictions.

Methods: This retrospective cohort study included adult patients with NSTIs admitted to the intensive care unit (ICU) of the University Hospital Zurich, Switzerland, from July 2008 to December 2023. NSTI cases were categorized as pre-, during, and postrestrictions. The primary outcome was the proportion of GAS in NSTI, and the exploratory secondary outcome was in-hospital death. A data analysis was conducted using Firth logistic regression adjusted for age, sex, diabetes, and initially affected body region.

Results: Overall, 74 NSTI cases were identified, with 49 occurring before, 8 during, and 17 after the pandemic restrictions. GAS was isolated in 27 (36%) cases, with 17 (35%) pre- and 10 (59%) postrestrictions, but none during the restrictions. NSTIs caused by other bacteria persisted during the restrictions. The odds of GAS were significantly lower during the restrictions (adjusted odds ratio, 0.02; 95% CI, 0.001-0.81) compared with after, while no significant differences were found between the pre- and postrestriction periods.

Conclusions: The significant decrease of GAS-NSTIs during the COVID-19 pandemic restrictions suggests that isolation measures may have prevented the transmission of GAS, resulting in a decline of GAS-NSTIs while NSTIs caused by bacteria transmitted by alternative routes persisted.

Background: Central skull base osteomyelitis (CSBO) is an incompletely defined, life-threatening infection of the bones of the cranial vault. We describe the clinical features and outcomes of CSBO in Queensland, Australia, over an 11-year period.

Methods: Medical record coding enquiries identified cases of CSBO across 6 tertiary hospitals in Queensland, Australia, from January 2010 to December 2020. Epidemiological, demographic, diagnostic, management, and outcome data were collected from each identified case.

Results: Twenty-two cases of CSBO were identified within the study period; the median age was 73 years with a male predominance (73%). High rates of comorbid disease were detected, with a median Charlson Comorbidity Index score of 5. Diabetes mellitus was the most frequently observed condition. Six cases had bone sampling for microbiological diagnosis while the remainder had superficial sampling of contiguous structures. The most common pathogen isolated was Pseudomonas aeruginosa followed by Staphylococcus aureus, with only 1 case of fungal infection. This series demonstrated a mortality rate of 31.8%, with 45.5% of cases left with long-term sequelae including persistent pain and cranial nerve deficits.

Conclusions: Four key observations emerged in this series: (1) advanced age and diabetes mellitus are common risk factors for CSBO, (2) limited surgical intervention occurred, (3) microbiological diagnoses relied primarily on superficial sampling, and (4) significant mortality and morbidity was observed. Prospective studies are needed to better understand the optimal approach to the diagnosis and management of CSBO and to improve clinical outcomes.

Background: People who inject drugs (PWID) are at risk of severe injection-related infection (SIRI), which is challenging to manage. We conducted a scoping review to map the existing evidence on management of PWID with SIRI in an outpatient setting.

Methods: We conducted a literature search in MEDLINE, Embase, Cochrane Central, and CINAHL from their inception until 6 December 2023. Studies were included if they focused on PWID with SIRI requiring ≥2 weeks of antibiotic therapy, with a proportion of management occurring outside hospitals. Studies were categorized inductively and described.

Results: The review included 68 articles with the following themes. PWID generally prefer outpatient management if deemed safe and effective. Most studies support outpatient management, finding it to be as effective and safe as inpatient care, as well as less costly. Successful transition to outpatient management requires multidisciplinary discharge planning with careful consideration of patient-specific factors. Emerging evidence supports the effectiveness and safety of outpatient parenteral antibiotic therapy, long-acting lipoglycopeptides, and oral antibiotic therapy, each having unique advantages and disadvantages. Various specialized outpatient settings, such as skilled nursing facilities and residential treatment centers, are available for management of these infections. Finally, all patients are likely to benefit from adjunctive addiction care.

Conclusions: Emerging evidence indicates that outpatient management is effective and safe for SIRI, which is preferred by most PWID. Key components of outpatient management include multidisciplinary discharge planning, appropriate antibiotic modality, suitable care settings, and adjunctive addiction care. These elements should be carefully tailored to patient needs and circumstances.

Background: International consensus definitions for invasive aspergillosis (IA) in research are rigorous, yet clinically significant cases are often excluded from clinical studies for not meeting proven/probable IA case definitions. To better understand reasons for the failure to meet criteria for proven/probable infection, we herein review 47 such cases for their clinical and microbiological characteristics and outcomes.

Methods: Data on 47 cases that did not meet consensus IA definitions but were deemed significant were derived from a retrospective, observational, multicenter survey of 382 presumed IA cases across Australasia, of which findings of 221 proven/probable infections were recently published. The clinical, microbiological, and radiologic characteristics of these cases were analyzed. Mortality outcomes were compared with those of 221 proven/probable cases.

Results: Of 47 cases studied, 15 lacked classical host factors; 22 exhibited only a single positive Aspergillus polymerase chain reaction result; 7 lacked typical IA radiologic findings on chest computed tomography; and 3 had borderline galactomannan optical density indices (<1.0 but ≥0.5) in bronchoalveolar lavage fluid. The median age of patients was 61 years (IQR, 52-68); 34 were male (72%). Seven patients (15%) required intensive care admission. All patients had lung as the primary site of infection. Antifungal treatment was initiated in 42 patients (89%). All-cause 90-day mortality was 33%, similar to the 30% mortality in the comparative cohort (n = 221).

Conclusions: Our findings highlight the limitations of current consensus definitions for IA. Notably, the mortality of patients not meeting these definitions was similar to that of patients with proven/probable IA. Further studies, especially of patients with a single positive Aspergillus polymerase chain reaction result and those without host factors, are needed to determine if future consensus definitions may benefit from modifications.

Background: Cryptococcal meningitis (CM) is responsible for 15%-20% of human immunodeficiency virus (HIV)-associated mortalities. CM prevalence has also increased in other immunocompromised populations of transplant recipients, patients with cancer, and individuals on immunomodulatory medication.

Methods: This retrospective review included 51 definitive patients with CM hospitalized at a tertiary academic medical center in New York City between 2010 and 2023. We assessed clinical features and outcomes of CM, with additional analysis of factors related to antiretroviral therapy (ART) adherence in HIV-infected cases and immunomodulatory medication history of HIV-negative cases.

Results: The cohort had a mean (standard deviation) age of 47.1 ± 15.1 years, and was predominantly male (37, 72.5%). Of 32 patients with HIV, 3 (9.4%) were newly diagnosed with HIV at the time of CM hospitalization, 5 (15.6%) had recurrent CM, and 2 (6.3%) had a CM relapse. The majority (30, 93.8%) of patients with HIV were ART nonadherent. Of 19 HIV-negative patients, 8 (42.1%) were solid-organ transplant recipients, 5 (26.3%) had autoimmune conditions of sarcoidosis or systemic lupus erythematosus, and 3 (15.8%) had chronic lymphocytic leukemia. Six (11.8%) patients died during hospitalization, 4 of whom had HIV.

Conclusions: The burden of CM in people with HIV and immunocompromised patients continues even in settings with accessible standard antifungal treatment though interventions of increased ART adherence for those with HIV and antifungal prophylaxis may improve morbidity and mortality.