Open Forum Infectious Diseases最新文献

Long-acting injectable (LAI) antiretroviral therapy (ART) is a promising option for people with HIV who face persistent adherence challenges, though literature to support its use in cases of integrase strand transfer inhibitor (INSTI) resistance remains limited. We describe a 36-year-old man with advanced HIV-1, long-standing nonadherence to oral medications, and virologic failure who harbored both an INSTI major mutation (E92Q) and accessory mutation (E157Q). Given persistent nonadherence and viremia, he was started on dual LAI lenacapavir plus cabotegravir/rilpivirine. His viral load declined to 143 copies/mL within 6 weeks after initiation of injectable ART and has remained undetectable thereafter. This case suggests that dual LAI ART may be effective in certain cases of underlying INSTI resistance and highlights the need for further study of this novel regimen in treatment-experienced individuals.

Background: Cystic fibrosis (CF) pulmonary exacerbations shorten survival. Treatment guidelines omit minimal inhibitory concentration (MIC)-based antibiotic dose selection. We tested whether MIC-guided intravenous antibiotic strategies prolong time between exacerbations.

Methods: We retrospectively studied randomly chosen intravenous antibiotic-treated pulmonary exacerbations from 2015 to 2018, followed through 2021. Using pre-admission sputum culture-derived MICs to select dosing targets, we estimated measured:target ratios for β-lactam steady-state and aminoglycoside area under the curve pharmacokinetics. We used Kaplan-Meier and Cox proportional hazards methods to test whether measured:target ratios were associated with time to next exacerbation. We evaluated serial laboratory measurements with linear mixed-effects models for adverse events. We tested model sensitivities to concurrent treatments and severe acute respiratory syndrome coronavirus 2 pandemic-related events.

Results: Compared with measured:target ratios ≤1, β-lactam ratios >1 were associated with a median of 19 more (from 204 to 223) exacerbation-free days (91 exacerbations; hazard ratio [HR], 0.60; 95% CI, 0.37-0.99; P = .045); aminoglycoside ratios >1 were associated with a median of 83 more (from 153 to 236) exacerbation-free days (65 exacerbations; HR, 0.54; 95% CI, 0.31-0.93; P = .026); both antibiotic ratios >1 simultaneously were associated with a median of 210 more (from 185 to 396) exacerbation-free days (60 exacerbations; HR, 0.33; 95% CI, 0.15-0.71; P = .004). No toxic antibiotic levels and few adverse laboratory or clinical events occurred. Models were insensitive to other treatments and pandemic events.

Conclusions: MIC-guided antibiotic dosing prolongs time between pulmonary exacerbations with few adverse events. Reduced exacerbation frequency predicts better survival and may improve quality of life for people with CF.

Background: The success of malaria elimination in sub-Saharan Africa rests largely on the sustained efficacies of the chemointerventions used in malaria treatment and chemoprophylaxis in the highest-burden countries such as Nigeria. Data on the impact of these interventions can guide policy for sustained malaria control toward elimination. We report the complexity of infection (number of genetically distinct same-species parasite strains observed in an infection) and genetic diversity of Plasmodium falciparum in Nigeria and their antimalarial resistance profiles.

Methods: We used targeted amplicon sequencing techniques to analyze 895 P falciparum clinical isolates collected from the 6 geopolitical zones of Nigeria, mostly between 2017 and 2021. Genotypes from 101 single-nucleotide polymorphisms and 36 nonsynonymous amino acid mutations associated with antimalarial drug resistance were used to determine the complexity of infection, the haplotypes of drug resistance genetic markers, genetic diversity, and pairwise relatedness of infections, according to R packages.

Results: Overall, infections were highly complex, with approximately 30% of these having more than a single genetically distinct parasite clone. Furthermore, 55.1% of the parasite isolates carried wild type alleles of the chloroquine transporter gene Pfcrt at codons 74 to 76. Highly related chloroquine-sensitive infections were observed in recent infections in several sites, especially Bauchi. However, the chloroquine-resistant haplotype CVIET persisted in 40.9% of infections, 26.5% of which were monoclonal and 14.4% were mixed. Sulfadoxine-pyrimethamine resistance alleles (codons 51, 59, and 108) at Pfdhfr loci were observed in >50% of infections, while the Pfdhps A437G mutation was detected in 87.3%. Most infections were wild type at Pfkelch13, although 12 nonsynonymous propeller domain mutations were observed.

Conclusions: Chloroquine sensitivity at the molecular level is now dominant in Nigeria, while antifolate resistance persists. Enhanced molecular surveillance of drug resistance-associated loci will serve as an early warning to safeguard the efficacy of chemointerventions in Nigeria.

Background: Bone and joint infections (BJIs) are increasingly reported worldwide, but data on their epidemiology remain limited in tropical settings. We aimed to characterize the causative agents of BJIs and their resistance patterns, in order to inform empirical antibiotic in our tropical setting.

Methods: This 6-year retrospective study included all adults with a first microbiologically confirmed episode of BJI between January 2019 and December 2024 at the Guadeloupe University Hospital, a tertiary care center in the Caribbean.

Results: A total of 312 patients with BJI were included. Among the 449 isolates recovered, Gram-negative bacilli (GNB) were predominant (41%), including AmpC β-lactamase-producing Enterobacterales (13%, 59/449) and Pseudomonas aeruginosa (9%, 39/449). Methicillin-resistant Staphylococcus aureus accounted for 3% (13/449). At least one GNB was identified in 31% of native septic arthritis (27/88), 33% of spondylodiscitis (9/27), 38% of prosthetic joint infections (27/71), 47% of osteosynthesis-associated infections (48/103), and 52% of osteomyelitis (12/23). Factors independently associated with GNB infection were a history of bite/scratch wound, contact with soil/vegetation and lower limb infection. Cefazolin provided limited likelihood of in vitro adequacy against causal pathogens in native septic arthritis episodes (74%, as compared to 92% for both cefepime and piperacillin-tazobactam). Lower rates were observed in cases of osteosynthesis-associated and prosthetic joint infections (48%-68%, as compared to 62%-75% for third-generation cephalosporins, 79%-80% for cefepime and 80%-86% for piperacillin-tazobactam).

Conclusions: Our findings highlight the prominent role of GNBs in tropical BJI and support the implementation of local surveillance systems to guide empirical treatment strategies.

Background: Although failure of rabies postexposure prophylaxis is rare, several factors, including improper vaccine or rabies immunoglobulin administration, may increase the risk. Where there is the potential for postexposure prophylaxis failure, public health units may recommend serology to confirm a therapeutic immune response. This study evaluates which factors increase the risk of failed seroconversion in cases where serology was indicated after rabies postexposure prophylaxis.

Methods: Potential lyssavirus exposure notifications where serology was collected were identified from 5 Southeast Queensland public health units from June 2015 to December 2022. Data on the indication and outcome of serology were extracted from public health case notes. Descriptive analysis was performed comparing serology outcomes by demographic and PEP course characteristics. Modeling for identified risk factors was conducted using hierarchical selection logistic regression analysis.

Results: One hundred eighty-one potential exposures were included in the study. Giving a rabies vaccine in the wrong site (relative risk [RR], 10.8; 95% CI, 2.6-36.4) or a vaccine into the same arm within 72 hours of rabies immunoglobulin (RR, 5.6; 95% CI, 1.9-16.9) increased the risk of nontherapeutic serology after adjusting for age and serology indication. Age ≥65 also increased the risk of nontherapeutic serology after controlling for administration errors (RR, 4.0; 95% CI, 1.3-11.7).

Conclusions: Administering rabies vaccine into an incorrect site or into the same arm within 72 hours of rabies immunoglobulin increases the risk of failed seroconversion. In such cases, we recommend that the risk is sufficient to invalidate the dose and immediately repeat it without serology. Older age may be an independent risk factor for failed seroconversion.

Background: Febrile illness is a leading cause of morbidity and mortality among children in low- and middle-income countries, yet the spatial distribution and environmental drivers of pediatric fever in Uganda remain poorly characterized.

Methods: We analyzed data from the 2016 Uganda Demographic and Health Survey to estimate the prevalence of febrile illness among children under 5 years of age. Using a geostatistical binomial model, we evaluated associations between fever prevalence and environmental, nutritional, and sociodemographic covariates. Spatial prediction and model calibration were conducted using the PrevMap package in R, and model performance was assessed using nonrandomized probability integral transform (nrPIT) and theoretical variograms.

Results: Among 14 195 children from 685 clusters, 4990 (35.1%) were reported to have had fever in the prior 2 weeks. Predicted fever prevalence varied substantially by region and month, with highest rates in the eastern and northeastern regions and in the period following the rainy season. Covariates including poverty, anemia, rainfall (2-month lag), enhanced vegetation index (1-month lag), and seasonality significantly improved model performance and reduced spatial uncertainty.

Conclusions: Our findings reveal pronounced geographic and temporal heterogeneity in pediatric febrile illness in Uganda. Environmental and nutritional factors significantly contribute to this variation. These results support targeted, region-specific public health interventions and inform future research into the etiologic drivers of pediatric fever.

Background: While disparities in COVID-19 therapeutic access have been documented, the effect of HIV status on treatment access and how it intersects with other sociodemographic factors has not been well explored. Using data from the National Clinical Cohort Collaborative (N3C), we investigated disparities in COVID-19 therapeutic prescription among persons with HIV and without HIV.

Methods: This was a retrospective cohort study of patients' data from January 2020 to November 2024. The study included 7 806 412 patients with a COVID-19 diagnosis, of whom 45 508 (0.58%) were persons with HIV. We employed logistic and linear regression models to assess associations between therapeutic receipt and patient characteristics.

Results: Persons with HIV had significantly higher adjusted odds of receiving COVID-19 therapeutics compared to persons without HIV (remdesivir, aOR 1.26 [95% CI: 1.20, 1.33]; nirmatrelvir/ritonavir, aOR 2.86 [95% CI: 2.77, 2.95]). Despite this, significant racial/ethnic inequities were observed. American Indian or Alaskan Native persons with HIV (estimated coefficient 0.997) and Hispanic/Latinx persons with HIV (estimated coefficient 0.992) had a lower estimated prevalence of remdesivir receipt compared to White Non-Hispanic individuals. For nirmatrelvir/ritonavir, Black/African American individuals (persons with HIV, estimated coefficient 0.947; persons without HIV, estimated coefficient 0.943), American Indian or Alaskan Native persons with HIV (estimated coefficient 0.996), and Hispanic/Latinx individuals (estimated coefficient 0.992) showed a lower estimated prevalence of receipt compared to their White counterparts.

Conclusions: Persons with HIV demonstrated higher odds of receiving COVID-19 therapeutics than persons without HIV. However, persistent racial and ethnic inequities in treatment uptake were evident.

Background: Outcomes of patients with acute pyelonephritis (AP) treated in a hospital-at-home setting have not been comprehensively evaluated in the United States.

Methods: We performed a multicenter, retrospective cohort study of adults diagnosed with and managed for AP in Mayo Clinic's Advanced Care at Home (ACH) program between July 2020 and January 2025. Collected data included demographics, Charlson Comorbidity Index (CCI), genitourinary comorbidities, severity of illness (SOI), and risk of mortality (ROM) scores, as well as pyelonephritis-related complications. Outcomes included length of stay (LOS), escalation of care, and 30-day postdischarge emergency department (ED) visits, readmissions, and mortality.

Results: A total of 165 patients met inclusion criteria. Median age was 67 years; SOI scores were moderate in 33.3%, major in 52.1%, and extreme in 8.5%. ROM scores were moderate in 30.3%, major in 38.2%, and extreme in 6.7%. Median CCI score was 5, and all patients had preexisting genitourinary conditions. On admission, 30.9% met sepsis criteria, acute kidney injury was present in 47.3%, and bacteremia developed in 33.3%. Median LOS in the ACH program was 3.1 days. Only 4.8% required escalation to a brick-and-mortar hospital. Readmission occurred in 17.0%, and 4.8% had ED visits. No in-program deaths occurred.

Conclusions: This multicenter retrospective study shows that AP, including cases with high illness severity and complex comorbidities, can be managed safely and effectively in a hospital-at-home setting with careful patient selection and robust infrastructure to support timely escalation when needed.

Vaccine effectiveness of BNT162b2 KP.2 vaccine against COVID-19 hospital admissions was 49% (95% CI, 30-63) and 45% (95% CI, 35-54) against emergency department/urgent care encounters (vs no KP.2 vaccine at <3 months). Protection persisted >90 days from vaccination with some waning. Vaccine effectiveness remained high regardless of prior COVID-19 vaccination and among older adults.

Background: In many resource-limited settings, hospitalization for community-acquired infection is common, but data regarding illness severity, etiology, and morbidity remain sparse.

Methods: We conducted a prospective observational study from May 2022 to August 2023 at 2 hospitals in northeast Thailand. Adults hospitalized with community-acquired infection were enrolled within 24 hours of admission and followed up to 28 days. We identified patients meeting sepsis criteria and assessed related epidemiology, management, and mortality risk factors.

Results: Of 1445 patients screened, 940 were enrolled. The median age was 60 years and preexisting diabetes mellitus was common (42%). Sixty-six percent of patients met sepsis criteria. Blood cultures and broad-spectrum antibiotics on admission were common (both >95%), although lactate measurement was performed in 43% of patients with sepsis. In patients with sepsis, critical illness outside the intensive care unit was common on medical ward admission, including respiratory failure (33%) and shock (21%). Tropical etiologies of infection included melioidosis (8%) and leptospirosis (4%), and gram-negative organisms accounted for 81% of bacteremia. Twenty percent of patients with sepsis died by 28 days. Sepsis-associated acute kidney injury (SA-AKI) on admission was independently associated with mortality (adjusted odds ratio, 2.07; 95% CI, 1.30-3.29; P = .002), and patients with SA-AKI had worse survival (P < .001) than those without.

Conclusions: In rural Southeast Asia, sepsis is common among patients hospitalized with infection and associated with substantial morbidity and mortality. Distinct pathogens and broad-spectrum antibiotics are common, even in the absence of sepsis. We identified several modifiable risk factors of death, including SA-AKI, potentially influencing initial management in similar settings.