Infectious Diseases and Therapy最新文献

Introduction: Acute gastroenteritis (AGE) represents a significant global health burden, with enteric viruses being a leading cause of gastroenteritis worldwide. Despite advances in diagnosis and treatment, there are limited data on adults seeking care due to AGE of viral etiology. This study aimed to describe the etiological, clinical, and epidemiological characteristics of viral AGE in adult patients presenting for medical consultation in a tertiary hospital over a 2-year period.

Methods: A retrospective cross-sectional study was conducted, with 8886 stool samples from 8356 adult patients presenting acute diarrhea between January 2021 and December 2022. A molecular real-time RT-PCR panel was used to screen for common bacterial, parasitic, and viral pathogens. Clinical and demographic data were collected, and statistical analysis was performed to evaluate possible associations.

Results: Enteric viruses constituted 10.3% (307 cases) of all AGE of known etiology, with norovirus being the predominant pathogen (196, 63.8%), followed by rotavirus (82, 26.7%) and adenovirus (29, 9.4%). The different viruses showed a distinct seasonal predominance. Coinfection with other microorganisms was common. Most cases exhibited a self-limiting course. Mortality and hospitalization rates were high in patients with higher comorbidity indices, mainly in individuals with immunosuppression.

Conclusions: Viruses are an important cause of acute gastroenteritis in adults presenting for medical consultation. The new multiplex molecular tests with high sensitivity and specificity allow early differential diagnosis in AGE. It is therefore necessary to identify which special populations particularly with higher comorbidity indices, would benefit from the implementation of these techniques, to guide decision-making related to appropriate treatments and avoid unnecessary interventions.

Introduction: The host range of phages is usually assessed with the agar overlay method. However, this method is both cumbersome and subjective. Therefore, a microbroth assay was developed to assess host range and lytic activity patterns of phages in the agar overlay method against a collection of carbapenemase-producing Klebsiella pneumoniae (CRKP) isolates.

Methods: The host range of 11 K. pneumoniae-specific phages against 8 non-repetitive well-characterized CRKP isolates was assessed with the agar overlay method and a microbroth assay by monitoring optical density (OD) at 630 nm for 24 h at different phage concentrations (5 × 10⁹-5 × 10³ PFU/ml) and two bacterial inocula (5 × 10⁶ and 5 × 10⁸ CFU/ml). The lytic activity of phage-bacteria pairs with transparent/semi-transparent (N = 7), turbid (N = 6), and no (N = 6) lysis in overlay agar method was compared statistically with the growth inhibition at 6 and 24 h in the microbroth assay with analysis of variance (ANOVA), receiver operating characteristic curves (ROC) curves and Fisher's exact test. Optimal cutoffs were determined, and sensitivity and specificity were calculated.

Results: Statistically significant differences of growth inhibition at 6 and 24 h for phage concentrations ≥ 5 × 10⁸ PFU/ml for both inocula were found between phages with transparent/semi-transparent, turbid, and no lysis. ROC curve analysis indicated an optimal growth inhibition cutoff of ≥ 31% at high phage and bacteria concentrations for detecting phages with lysis and ≥ 61% at high-phage and low-bacteria concentrations for detecting phages with transparent/semi-transparent lysis with sensitivity/specificity 100%/100% and 100%/86%, respectively.

Conclusions: The microbroth growth inhibition assay provided fast, reliable, and objective results for K. pneumoniae phage host-range lytic activity differentiating different patterns of lysis in a high-throughput format.

Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a guiding principle during pregnancy. Dolutegravir/lamivudine (DTG/3TC) has demonstrated high efficacy, a high barrier to resistance, and a good safety profile in non-pregnant individuals; however, DTG/3TC is not recommended by perinatal HIV treatment guidelines for initial therapy in pregnant people living with HIV-1 because of limited data on use of the 2-drug regimen during pregnancy. Efficacy and pharmacokinetic data from pregnant individuals using DTG and/or 3TC are reviewed and used to extrapolate anticipated DTG/3TC efficacy in pregnancy. There are robust data on the use of DTG- and 3TC-containing combination regimens, which are recommended by perinatal HIV treatment guidelines during pregnancy, supporting their well-established efficacy and safety in pregnant people living with HIV-1. Updated data from the Tsepamo and Eswatini surveillance studies (> 14,000 DTG exposures from conception) indicate no increased risk of neural tube defects with DTG. Pharmacokinetic data for DTG and 3TC indicate that exposures in pregnancy are within the therapeutically effective range seen in non-pregnant adults. Two studies evaluated DTG/3TC during pregnancy and both reported high virologic suppression rates [HIV-1 ribonucleic acid (RNA) < 50 copies/mL at delivery: 97% (30/31) overall], no events of vertical transmission, and no new safety signals, consistent with the use of DTG-based 3-drug regimens in pregnancy. The use of DTG/3TC during pregnancy is anticipated to be comparably effective and well tolerated for both parental health and prevention of vertical transmission with fetal exposure to fewer antiretrovirals compared with 3- or 4-drug regimens. These considerations are relevant when evaluating use of DTG/3TC in people living with HIV-1 who are pregnant or considering pregnancy in clinical practice and in perinatal HIV treatment guidelines.Video abstract available for this article. Supplementary file1 (MP4 319,147 KB).

Introduction: There remains uncertainty about whether transitioning to oral antibiotic therapy is appropriate for the management of children with methicillin-resistant Staphylococcus aureus (MRSA) bacteremic osteomyelitis. We compared clinical outcomes for children with MRSA osteomyelitis with associated bacteremia who were transitioned to discharge oral antibiotic therapy to those discharged on outpatient parenteral antibiotic therapy (OPAT).

Methods: We performed a retrospective, multicenter, cohort study of children ≤ 18 years hospitalized with MRSA bacteremic osteomyelitis across four children's hospitals from 2007 to 2018 discharged on oral antibiotic therapy versus OPAT. The primary outcome was treatment failure within 6 months of discharge, defined as any of the following: diagnosis of chronic osteomyelitis, conversion from oral to IV antibiotic route, an operative procedure after the index hospitalization (abscess drainage, bone biopsy, arthrocentesis, or pathologic fracture) and/or recrudescence of MRSA bacteremia. Outcomes were analyzed in an inverse propensity score weighted (IPW) cohort.

Results: A total of 106 cases of MRSA bacteremic osteomyelitis were included; 44 (42%) were discharged in the oral antibiotic therapy group and 62 (59%) patients were discharged in the OPAT group. In the IPW cohort, treatment failure within 6 months of discharge occurred in 3.4% of children in the discharge oral therapy group and 16.3% in the OPAT group (P = 0.03). The odds of 6-month composite treatment failure between discharge oral therapy and OPAT were 0.18 (95% CI 0.05-0.61).

Conclusions: Discharge oral therapy was not associated with higher rates of treatment failure compared to OPAT for children with MRSA bacteremic osteomyelitis.

Introduction: Amphotericin B lipid complex (ABLC) is an effective antifungal agent for treating invasive fungal infections (IFIs) even though its formulation is associated with potential adverse events, including those related to its infusion. This study aimed to analyze the incidence of acute infusion-related side effects (IRSE) associated with ABLC and their relationship with the profile of patients with oncohematological disease admitted in Brazilian reference tertiary hospitals.

Methods: This is an observational retrospective study that included clinical records of patients hospitalized, in a period of 6 years, diagnosed with probable or proved IFI and treated with at least two doses of ABLC.

Results: A total of 229 patients were included, with a male prevalence and an average age of 44 years for adults and 10 years for children. Seventy-nine (34.5%) developed some IRSE, 5.1% of which progressed in severe form to discontinuation of treatment. The most prevalent events in adults were fever (66.7%), tremor/chills (53.3%), and tachycardia (24.4%). In children, the most common were fever (64.7%), tremors/chills (50%), and skin rash/itching (17.6%). Statistical significance was found for premedication use from the first dose of ABLC in relation to the onset of infusion reactions (P = 0.006). Multivariate analysis revealed that ABLC, when compared to liposomal AMB (L-AMB), and neutropenia were associated with a higher risk of developing IRSE (odds ratio [OR] 3.04, P = 0.008; and OR 11.02, P = 0.025, respectively).

Conclusions: The use of premedication was a protective factor against the occurrence of IRSE. Therefore, services providing amphotericin B (AMB) must reinforce protocols or implement new measures that optimize tolerability and safety during the treatment of patients with oncohematological disease, with special attention to patients with neutropenia, prioritizing the liposomal formulation of AMB whenever possible.

Introduction: Despite achieving sustained viral response (SVR) after treatment with direct-acting antivirals (DAAs), the risk of liver disease progression and extrahepatic complications in chronic hepatitis C (CHC) remains. We aimed to determine the role of residual HCV-RNA in peripheral blood mononuclear cells (PBMCs), a condition known as occult hepatitis C (OCI), and systemic inflammatory markers as predictors of long-term outcomes in patients treated with DAAs.

Methods: We followed 42 patients treated with DAAs with OCI status determined after therapy, for a median of 6.3 years. Plasma levels of 16 cytokines and chemokines were measured in samples collected 12-15 months after end of treatment. Samples from 10 patients with CHC and 8 healthy controls were used for comparison.

Results: The presence of HCV-RNA in PBMCs correlated with adverse outcomes [odds ratio (OR) 17.6, confidence interval (CI) 1.8-175); p = 0.011], and an elevated platelet-to-lymphocyte ratio (PLR) was associated with mortality. Patients with residual HCV-RNA had higher levels of macrophage-derived chemokine (MDC/CCL22) (p = 0.026) and interleukin-18 (IL-18) (p = 0.009), but lower levels of fractalkine/CX3CL1 (p = 0.007), interferon gamma (IFNγ) (p = 0.016), IL-13 (p = 0.009), and lymphotoxin alpha (LTα) (p = 0.007) compared to those without OCI. The profile of immune mediators in patients with OCI differed more from healthy controls than from patients without OCI.

Conclusions: These findings suggest that residual HCV-RNA and elevated PLR are potential predictors of poor long-term outcomes in patients treated with DAAs, possibly linked to an altered cytokine/chemokine response.

Introduction: Real-world data from multinational observational studies are required to better understand the role and performance of isavuconazole in real-world practice in Europe.

Methods: A retrospective medical record review was conducted at 16 sites in Europe (France, Germany, Italy, Spain, and the United Kingdom). Eligible records were from patients aged ≥ 18 years at the time of isavuconazole initiation and received at least one dose of isavuconazole for suspected or confirmed invasive aspergillosis (IA) or invasive mucormycosis (IM) during the eligibility period (October 15, 2015 to June 30, 2019). Data were descriptively analysed. Success rates, overall survival, and times to these events were descriptively analysed.

Results: Data were abstracted from 218 patients (201, IA; 17, IM) who received isavuconazole as monotherapy (initiated as infusion, 52%; oral, 46%). Isavuconazole was initiated as primary therapy in 92 patients (42.2%) and salvage therapy in 121 patients (55.5%) (unknown for five patients). Mean (standard deviation) age was 56.8 (15.6) years, 66% were men and 62% had at least three comorbidities, most frequently haematologic malignancy (62%). Estimated clinical response rate at week 24 was 54.5% (95% confidence interval [CI], 38.2-66.5%) for primary treatment and 73.5% (95% CI, 62.7-81.1%) for salvage therapy. Overall, 45 patients (21%) experienced at least one adverse event (AE). Serious AEs were experienced by 37 patients (17%), with seven related to isavuconazole; five patients (2.3%) discontinued isavuconazole monotherapy due to the serious AE. A total of 137 patients (63%) died, with 17 deaths (12.4%) related to their invasive fungal infection, 11 of whom initiated isavuconazole as salvage therapy.

Conclusions: This study adds to the growing body of evidence that whether used as first-line therapy or after the failure of other antifungal therapies, isavuconazole appears to have a promising clinical response and a good safety profile as an antifungal agent in patients with varied underlying conditions.

Introduction: This study characterized the population pharmacokinetics (PK) of vancomycin in patients treated with and without continuous renal replacement therapy (CRRT) or temporary mechanical circulatory support (tMCS), including extracorporeal membrane oxygenation or extracorporeal ventricular assist device.

Methods: Critically ill adults with and without tMCS or CRRT prescribed vancomycin were enrolled for population PK modeling. Monte Carlo simulation provided dosing recommendations based on the probability of target attainment (PTA), achieving a 24-h area under curve (AUC24h) of 400-600 mg*h/L.

Results: Twenty-five patients with 184 plasma samples were analyzed. The median age was 61.0 years. The final model was a two-compartment PK model. CRRT, serum creatinine, and body weight were significant predictors of clearance. CRRT was a covariate on the central volume of distribution. tMCS significantly decreased the intercompartmental clearance. The simulated mean trough levels at the 48th hour were lower in the tMCS group (13.4 versus 14.2 mg/dL in non-tMCS, p < 0.001) in a 70-kg subject with a creatinine of 1 mg/dL and a daily dose of 20 mg/kg, but the PTA was similar (61.8% versus 62.2%). A reduction of maintenance dose from 30 to 10 mg/kg/day with loading dose from 25 to 15 mg/kg is recommended while serum creatinine progresses from 0.5 to 4.0 mg/dL. For CRRT, the optimal regimen consists of 20-25 mg/kg loading and maintenance of 15 mg/kg/day.

Conclusions: The dosing strategy of vancomycin can be based on body weight or renal function, regardless of tMCS. Intercompartmental clearance decreases under tMCS, which can mislead a dosing adjustment based on trough level.

Introduction: Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations.

Materials and methods: This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14 days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72 h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy.

Results: A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47 years for the IV-start group and 44 years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]).

Conclusion: Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies.

Trial registration: Clinicaltrials.gov, NCT02378480 and NCT02877927.