Infection最新文献

Purpose: To describe and characterize the evolutionary process of cross-resistance to ceftazidime/avibactam, ceftolozane/tazobactam and imipenem/relebactam of a carbapenem-resistant Pseudomonas aeruginosa (CRPA) lineage isolated from a patient receiving two courses of ceftazidime/avibactam treatment.

Methods: The minimum inhibitory concentrations (MICs) of strains were determined by broth microdilution methods. The mutant genes were identified by the whole genome sequencing results. Cloning, knockout and complementation experiments were used to evaluate the impact of the resistance relative genes on the MICs. Reverse transcription-quantitative PCR was used to evaluate the relative expression of ampC and mexA. The fitness cost was measured by growth curve tests.

Results: A total of 24 CRPA strains were isolated encompassing the whole ceftazidime/avibactam treatment. The CRPA strains developed high-level resistance to ceftazidime/avibactam and cross-resistance to ceftolozane/tazobactam or imipenem/relebactam, clustering into clade A and clade B, respectively. In both clades, the overexpression of AmpC was crucial to ceftazidime/avibactam resistance, which was driven by AmpD deficiency in clade A and dacB mutation in clade B, respectively. In clade A, mraY mutation and a new allele of AmpC (bla_PDC-575) elevated resistance to ceftazidime/avibactam, with bla_PDC-575 also conferring resistance to ceftolozane/tazobactam. In clade B, mexB mutation was associated with the resistance to both ceftazidime/avibactam and imipenem/relebactam. Moreover, the fitness costs of P. aeruginosa strains typically increased with the higher MICs of ceftazidime/avibactam.

Conclusion: Divergent resistance evolution resulted in a complex phenotype in the CRPA lineage, posing significant challenge to clinical treatment. The resistance surveillance needs to be prioritized, and new therapeutic strategies are urgently required.

Mycobacterium tuberculosis (M. tuberculosis) infection is the most common opportunistic infection in human immunodeficiency virus-1 (HIV-1)-infected individuals, and the mutual reinforcement of these two pathogens may accelerate disease progression and lead to rapid mortality. Therefore, HIV-1/M. tuberculosis coinfection is one of the major global public health concerns. HIV-1 infection is the greatest risk factor for M. tuberculosis infection and increases the likelihood of endogenous relapse and exogenous reinfection with M. tuberculosis. Moreover, M. tuberculosis further increases HIV-1 replication and the occurrence of chronic immune activation, accelerating the progression of HIV-1 disease. Exploring the pathogenesis of HIV-1/M. tuberculosis coinfections is essential for the development of novel treatments to reduce the global burden of tuberculosis. Innate immunity, which is the first line of host immune defense, plays a critical role in resisting HIV-1 and M. tuberculosis infections. The role of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway, which is a major DNA-sensing innate immune signaling pathway, in HIV-1 infection and M. tuberculosis infection has been intensively studied. This paper reviews the role of the cGAS-STING signaling pathway in HIV-1 infection and M. tuberculosis infection and discusses the possible role of this pathway in HIV-1/M. tuberculosis coinfection to provide new insight into the pathogenesis of HIV-1/M. tuberculosis coinfection and the development of novel therapeutic strategies.

Purpose: As certain vaccine serotypes are still circulating within the community during the PCV13 era, we aimed to delineate the clinical features and assess the immunity following breakthrough infections in children.

Methods: 101 PCVs-vaccinated children < 18 years with culture confirmed PCV13 serotype breakthrough infection (25/101, invasive pneumococcal disease [IPD]) was identified in Taiwan in 2015-2019. Immunoglobulin G (IgG) antibody levels, IgM⁺ memory B cells (MBCs), and isotype-switched immunoglobulin (sIg⁺) MBC specific to serotypes 3, 14, 19 A were assessed prior to and one month after an additional PCV13 booster in 9 patients. A cohort of 89 previously vaccinated, healthy children were enrolled as controls.

Results: The majority (88%) of the breakthrough infection occurred in children under 7 years old. Infection by serotypes 3 and 19 A increased in children aged 5-17 years in 2018-2019. The pre-booster serotype 3- and 19 A-specific IgG in both children with breakthrough infection and controls were lower than the IPD protective thresholds (2.83 µg/mL for 3; 1.00 µg/mL for 19 A). Breakthrough infected children showed higher geometric mean ratio in serotype-specific IgG, IgM⁺ MBCs and sIg⁺ MBC after an additional PCV13 booster, compared to the controls.

Conclusions: Most breakthrough infections occurred in previously healthy preschool-aged children, but such infections may still occur in school-aged children due to waning immunity. Breakthrough infections may also enhance the anamnestic response elicited by PCV13.

Background/objective: Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive.

Methods: Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999-2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30 days) and HIV-transmission routes were collected.

Results: In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36 years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29-40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17-20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20-24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29-32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts < 350.

Conclusion: This analysis characterizes HIV-ICs regarding the incidence, HIV-transmission route and patients' immune status. The results underline the importance of HIV-IC-based screening to detect PLWH with already partially impaired immune status and in need of timely ART initiation.

Purpose: C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment.

Methods: Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150 h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest.

Results: Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4 mg/L in viral infections without antibiotics to 140.9 mg/L in Gram-negative bacteremia with antibiotics.

Conclusions: CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients.

Purpose: Although guidelines recommend adjunctive rifampin and gentamicin use for patients with staphylococcal prosthetic valve endocarditis (PVE), evidence behind the recommendation is limited and conflicting.

Methods: We performed a retrospective cohort study of all patients with staphylococcal PVE within the Veterans Health Administration during 2003-2021. Patients were identified with diagnostic codes for prosthetic valves and positive blood cultures for Staphylococcus species and confirmed via manual chart reviews. The primary outcome was the composite of all-cause mortality or recurrence of staphylococcal PVE within one year from diagnosis. Inverse probability of treatment weighting (IPTW) was used to estimate the probability of individuals receiving rifampin using propensity scores. IPTW-adjusted multivariable Cox regression analysis was used to compare outcomes between patients who received rifampin and gentamicin, and those did not.

Results: Among 373 patients with staphylococcal PVE, 275 (73.7%) and 225 (60.3%) received at least one dose of rifampin and gentamicin, respectively. The incidence of staphylococcal PVE increased from 0.47 (2003-11) to 0.77 (2012-21) per 10,000 hospitalizations. Gentamicin use declined over time (70.1% in 2003-2011 to 54.8% in 2012-2021, p = 0.04) while rifampin use did not change significantly (76.1% in 2003-2011 to 72.4% in 2012-2021, p = 0.43). The composite outcome was observed in 209 (56.0%). Neither rifampin use (adjusted hazard ratio [HR] 0.77, 95% CI 0.48-1.24) and gentamicin use (adjusted HR 1.11, 95% CI 0.71-1.74) was associated with the composite outcome.

Conclusion: No significant association was observed between adjunctive rifampin or gentamicin use and improved outcomes.

Purpose: Antibiotics are often only available in predefined pack sizes, which may not align with guideline recommendations. This can result in leftover pills, leading to inappropriate self-medication or waste disposal, which can both foster the development of antibiotic resistance. The magnitude of inappropriate pack sizes is largely unknown. The objective of this study was to evaluate the potential non-conformity of prescribed antibiotic pack sizes.

Methods: This retrospective observational study was based on claims data from a large Swiss health insurance company. The study analysed the prescriptions of eleven different antibiotic substances recommended for the five most common indications for antibiotics in Switzerland. All prescriptions for adult outpatients issued by general practitioners in 2022 were included and extrapolated to the entire Swiss population. Potential non-conformity was defined as a mismatch between the total dosage in a pack and the total dosage recommended.

Results: A total of n = 947,439 extrapolated prescriptions were analysed. In 10 of 23 of all analysed substance/indication combinations none of the prescribed packs aligned with the respective guideline recommendation. Considering pack sizes in which the total prescribed dosage of a substance did not correspond to any of the total dosages recommended in at least one of the guidelines, 31.6% of prescriptions were potentially non-conform and an estimated number of 2.7 million tablets were overprescribed.

Conclusions: We found a large discrepancy between prescribed pack sizes and guideline recommendations. Since inadequately prepacked antibiotics may lead to antibiotic resistance and unnecessary waste, efforts are needed to implement alternatives like exact pill dispensing.

Purpose: The worldwide prevalence of Chagas Cardiomyopathy (CCM) as well as the trends in the prevalence of CCM over time have not been well characterized.

Methods: An analysis of the Global Burden of Disease (GBD) data from 1990 to 2019 was conducted to assess the burden of CCM. This study focused on determining the prevalence of CCM, along with its age-standardized prevalence rate (ASR) per 1,00,000 people, considering various patient demographics and geographical regions as defined in the GBD. Additionally, the study examined the temporal trends over this 30-year period by calculating the estimated annual percentage change (EAPC) in CCM prevalence for the global population and specific subgroups.

Results: Worldwide, the GBD reported 220,166 individuals with CCM in 1990 and 2,83,236 individuals in 2019, with a decline in the ASR from 5.23 (3.34-7.47) to 3.42 (2.2-4.91) per 1,00,000 individuals during that period. In 2019, the prevalence was highest in individuals over age 70 and in males compared to females. Among available geographic classifications in 2019, Latin American regions had the highest rates (ASR of 39.49-61.15/1,00,000), while high income North American and Western European regions had the lowest rates (ASRs of 0.67 and 0.34/1,00,000, respectively). Between 1990 and 2019, the worldwide prevalence of CCM per 1,00,000 decreased (EAPC of -0.35, -0.37 to -0.32), with similar trends among most regions and subgroups.

Conclusion: This analysis of the GBD data reveals both global and country-specific patterns in the prevalence and trends of CCM. Notably, CCM shows the highest prevalence in Latin American countries, although it's also significantly present in regions beyond Latin America. Notably, the global age-standardized rate of CCM is on the decline, suggesting improvements in healthcare strategies or lifestyle changes across the world.