Clinical Microbiology and Infection最新文献

Background: Healthcare-associated infections (HAIs) remain a significant challenge worldwide, and the use of multimodal strategies is recommended by the World Health Organization (WHO) to enhance infection prevention.

Objectives: To update the systematic review on facility-level infection prevention and control (IPC) interventions on the WHO Core Component of using multimodal strategies.

Methods: Data Sources: Medline (via PubMed), EMBASE, CINAHL, and the Cochrane library.

Study eligibility criteria: Randomized controlled studies (RCTs), interrupted time series (ITS), and before-after studies in acute care settings, from 24 November 2015 to 30 June 2023.

Participants: Both paediatric and adult populations.

Interventions: IPC interventions implemented with at least three WHO multimodality elements.

Primary outcomes: HAI, HAI caused by antimicrobial-resistant microorganisms, and hand hygiene (HH) compliance.Assessment of Risk of Bias: Effective practice and organisation of care (EPOC) and integrated quality criteria for review of multiple study designs (ICROMS) tools.Methods of data Synthesis: Descriptive data synthesis.

Results: Of 5678 identified titles and abstracts, 32 publications were eligible for data extraction and analysis. Five non-controlled before-after studies (NCBA) were excluded due to an insufficient ICROMS score. Of the remaining 27 studies, nine reported on the effect of multimodal strategies to reduce device-associated HAIs, four on surgical site infections, eight on infections due to AMR and six on HH compliance. Eleven were controlled studies (RCTs or controlled before-after studies (CBAs)), nine ITS and seven NCBA studies. Twenty-two of the studies originated from high-income countries and the overall quality was medium to low. Twenty studies showed either significant HAI-reductions or HH improvement.

Conclusion: Most studies demonstrate a significant effect on HAI prevention and HH improvement after applying a multimodal strategy. However, the quality of evidence remains low to moderate with few studies from low- or middle-income countries. Future research should focus on higher quality studies in resource limited settings.

Objectives: Because fungal infections (FI) are frequently encountered by pathologists, it is crucial to improve fungal diagnosis on formalin-fixed paraffin-embedded tissues (FT). We aimed to investigate if a histomolecular approach using targeted-massive parallel sequencing (MPS) could help detect and identify fungi on FT when no mycological diagnosis is available on fresh tissue.

Methods: Forty-nine FT from 48 patients with histopathological FI diagnosis but without mycological identification were retrospectively included. Histopathology defined the fungal pattern and the tissue injuries. Panfungal PCRs were performed using ITS-3/ITS-4 and MITS-2A/MITS-2B primers. Amplicons were sequenced using Sanger sequencing and targeted-MPS. Probabilities of fungal identification for both sequencing techniques and both primers were compared.

Results: The median age was 57 years (Q1: 47; Q3: 64). Fungal cultures were performed in 22/49 (44.9%) samples but failed to identify the pathogenic fungi. Fungal identification by Sanger sequencing was successful in 17/49 (34.7%; [0.214-0.480]) FT; the probability of fungal identification was 32.7% (16/49; [0.195-0.458]) for ITS-3/ITS-4; and 22.4% (11/49; [0.108-0.341]) for MITS-2A/MITS-2B. Targeted-MPS was successful in 35/49 (71.4%; [0.588-0.841]) samples; the probability of fungal identification was 59.2% (29/49; [0.454-0.729]) for ITS-3/ITS-4 primers and 61.2% (30/49; [0.476-0.749]) for MITS-2A/MITS-2B. The probability of fungal identification by targeted-MPS (35/49 [71.4%]) was significantly higher than that of Sanger sequencing (17/49 [34.7%]; p < 0.0001). We assessed that this approach could have optimized care for 22/48 (45.8%) patients.

Discussion: Integrated histomolecular diagnosis using targeted-MPS could secure diagnosis and help clinicians prescribe the most appropriate antifungal therapy in the absence of mycological identification.

Background: The World Health Organization (WHO) recommends antiretroviral therapy (ART) containing two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. WHO recommends tenofovir disoproxil fumarate combined with lamivudine or emtricitabine as first line in pregnancy, and zidovudine, abacavir or tenofovir alafenamide, combined with lamivudine or emtricitabine, as alternatives.

Objectives: Evaluate risk of adverse perinatal outcomes in pregnant women living with HIV (WLHIV) receiving different NRTIs.

Data sources: Medline, CINAHL, Global Health, EMBASE.

Study eligibility criteria: Cohort studies.

Participants: Pregnant WLHIV.

Interventions: ART regimes containing different NRTI drugs.

Assessment of risk of bias: Newcastle-Ottawa Scale and GRADE.

Methods of data synthesis: Random-effects meta-analysis.

Results: 22 cohort studies including 124,478 WLHIV met the eligibility criteria. ART containing tenofovir disoproxil fumarate was associated with lower risk of preterm birth (Risk Ratio 0.89; 95% confidence interval 0.81-0.97), very preterm birth (0.58; 0.40-0.86), small for gestational age (0.76; 0.59-0.98), very small for gestational age (0.60; 0.48-0.73), stillbirth (0.49; 0.31-0.78), and neonatal death (0.61; 0.40-0.93), compared to ART not containing tenofovir disoproxil fumarate. ART containing zidovudine was associated with increased risk of very preterm birth (1.59; 1.01-2.49), small for gestational age (1.33; 1.03-1.70), very small for gestational age (1.63; 1.25-2.13), stillbirth (2.23; 1.10-4.55), and neonatal death (1.65; 1.08-2.52), compared to ART not containing zidovudine. For ART regimens also containing either lamivudine or emtricitabine, zidovudine was associated with increased risk of very preterm birth (1.62; 1.04-2.52), small for gestational age (1.52; 1.28-1.82), very small for gestational age (1.68; 1.36-2.06), stillbirth (2.19; 1.03-4.67), and neonatal death (1.65; 1.08-2.52), compared to ART containing tenofovir disoproxil fumarate. Abacavir was not associated with adverse perinatal outcomes. Tenofovir alafenamide was not associated with low birth weight compared to tenofovir disoproxil fumarate.

Conclusion: Tenofovir disoproxil fumarate is associated with a lower risk of adverse perinatal outcomes, whereas zidovudine is associated with an increased risk of perinatal outcomes. Abacavir is not associated with adverse perinatal outcomes. Our findings support current WHO guidelines.

Objectives: To evaluate the impact of hospitalization for infectious diseases on the Health-Related Quality of life (HRQOL), multidimensional frailty, and functioning of older patients, we conducted a longitudinal matched cohort study in four European countries.

Methods: HRQOL, frailty, and functioning were assessed using validated questionnaires at inclusion, at discharge, and up to 6 months later in patients aged over 65 years hospitalized for severe acute respiratory or bloodstream infections, and matched controls hospitalized for non-infectious conditions. Comparative analyses employed multilevel mixed-effect linear or logistic models to assess changes from inclusion.

Results: Between 2020 and 2023, 1968 patients aged 65-100 years (mean, 81) were included; 1064 (54.1%) were male and 59 (3%) were institutionalized. Of these 1968 patients, 826 were hospitalized for infectious diseases and 1142 for non-infectious conditions. At inclusion, European Quality of Life 5 Dimensions and 3 Lines scores ranged from -0.7 to 1 (full HRQOL), with a median of 0.7 across all visits and groups. Compared with controls, patients hospitalized for infectious diseases had lower scores on the Activities of Daily Living (ADL) scale (median, 4.5 vs. 5.0; p 0.020) and the Instrumental ADL scale (median, 3.0vs. 4.0; p < 0.001). At discharge, Instrumental ADL scores were lower in patients hospitalized for infectious diseases than in controls (median, 4.0 vs. 5.0, p 0.003), indicating reduced functioning. The proportion of frail patients, determined by a Multidimensional Prognostic Index score between 0.67 and 1, was significantly higher among patients hospitalized for infectious diseases (n = 113/801, 14.1%) than controls (n = 108/1111, 9.7%; p 0.012). At six months, no statistically significant differences were observed between groups in changes from inclusion in HRQOL (European Quality of Life 5 Dimensions and 3 Lines, p 0.436), frailty (Multidimensional Prognostic Index, p 0.269), and functioning (ADL, p 0.993).

Discussion: Hospitalization for infectious diseases and non-infectious diseases or conditions had a similar impact on HRQOL in non-institutionalized older adults.

Objectives: The FOSFOMIC study assessed the clinical and microbiological effectiveness, and safety of intravenous fosfomycin in treating complicated urinary tract infections (cUTIs) caused by Escherichia coli, in comparison with other intravenous antimicrobials.

Methods: A prospective, multinational matched cohorts study involving adults with community-acquired cUTIs and receiving targeted therapy with intravenous fosfomycin or other first-line drugs (beta-lactams or fluoroquinolones) was conducted from November 2019 to May 2023 in ten centres from Spain, Italy, and Türkiye. Matching criteria included type of infection acquisition, Charlson and Pitt scores. Endpoints were clinical and microbiological cure, mortality, recurrence, and adverse effects. Analyses used conditional logistic regression and desirability of outcome ranking (DOOR).

Results: Overall, 155 matched pairs were included. Clinical and microbiological cure rates were 65.2% (101/155; 95% CI, 57.4-72.2) and 63.2% (98/155; 95% CI, 55.4-70.4) with fosfomycin and comparators, respectively (adjusted OR, 1.09; 95% CI, 0.68-1.73; p 0.73). Mortality rates were 1.9% (3/155; 95% CI, 0.7-5.5) and 5.8% (9/155; 95% CI, 3.1-10.7), respectively (p 0.11). Recurrence rates were 14.2% (22/155; 95% CI, 9.6-20.6) in the fosfomycin group vs. 10.3% (16/155; 95% CI, 6.1-16.1) (p 0.39). Severe adverse effects occurred in 1.9% (3/155; 95% CI, 0.7-5.5) of patients treated with fosfomycin vs. 0.6% (1/155; 95% CI, 0.0-3.3) in the control group (p 0.62). Non-severe adverse effects were more frequent with fosfomycin, affecting 23.3% (36/155; 95% CI, 17.0-30.7) compared with 7.7% (12/155; 95% CI, 4.1-13.1) in the control group (adjusted OR, 5.36; 95% CI, 2.04-14.1; p < 0.001). In DOOR analysis, fosfomycin demonstrated comparable effectiveness in treating pyelonephritis (probability of better DOOR, 54.0%; 95% CI, 48.5-59.6) and in comparison with ceftriaxone (50.3%; 95% CI, 44.7-55.8), without evidence of inferiority in bacteraemic urinary tract infections (DOOR, 47.3%; 95% CI, 41.7-52.8).

Discussion: Fosfomycin is a viable option for treating cUTIs caused by E. coli, allowing for diversification in the treatment of these high-incidence infections.

Objectives: The aim of this study was to develop a pharmacokinetic (PK) interaction model of intravenous (i.v.) and oral clindamycin when combined with rifampicin, and to determine whether appropriate clindamycin concentrations could be achieved for different doses and administration routes (oral, intermittent and continuous infusion) of clindamycin.

Methods: Five hundred and eighteen plasma samples were prospectively obtained from 124 patients treated for bone and joint infections. Population pharmacokinetic analysis was performed using Monolix software. Monte Carlo simulations were run to determine the probability of achieving a minimal clindamycin plasma concentration equal to at least twice the MIC, or an unbound area under the curve/MIC ≥60.

Results: A linear one-compartment model with first-order absorption and elimination was developed. Concomitant administration of rifampicin increased clindamycin clearance by an average factor of 3, whereas the impact on clindamycin bioavailability was dose dependent, with decreases from 56 to 11 and 4% for rifampicin doses of 600 mg and 900 mg q12 h, respectively. When administered simultaneously with rifampicin, satisfactory clindamycin concentrations could not be obtained when given orally. i.v. administration of a daily 3600 mg dose would be convenient for more than 80% of the patients, but doses of at least 4800 mg/d would be needed for a MIC equal to the 0.25 mg/L European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical breakpoint for Staphylococcus aureus. Intermittent i.v. administration every 6 hours is preferable to q8h regimens for the C_min/MIC criteria, but still performed poorly compared with continuous infusion.

Discussion: This model satisfyingly described the differential effect of rifampicin on the bioavailability and clearance of clindamycin. As previously described, this combination must not be taken orally. However, administration of clindamycin doses of at least 3600 mg/d by intermittent or, preferably, continuous infusion, can balance the impact of rifampicin.