Old foes following news ways?-Pandemic-related changes in the epidemiology of viral respiratory tract infections.

INTRODUCTION: Following lockdown periods and restricting public health measures in response to the COVID-19 pandemic, respiratory tract infections (RTIs) rose significantly worldwide. This led to an increased burden on children's hospitals compromising medical care of acutely and chronically ill children. We characterized changes in the epidemiological pattern of circulating respiratory viral infections. METHODS: We assessed the number of patients with RTIs and the annual distribution of virus detections between 2019 and 2022 based on 4809 clinical samples (4131 patients) from a German pediatric tertiary care-center. We investigated the impact of lockdown periods on spectra of circulating respiratory viruses, pattern of coinfections, age, and seasonality of infections. RESULTS: A fourfold increase in the number of respiratory virus detections was observed in 2022 vs 2019 with numbers doubling in 2022 (vs 2021). In 2022, seasonal patterns of circulating virus, particularly Adeno and seasonal Coronavirus were far less pronounced compared to previous years, in fact almost disappeared for Rhinoviruses.". SARS-CoV-2, Parainfluenza- and human Metapneumovirus detections increased significantly in 2022 (2019 vs 2022, p < 0.01). Coinfections with multiple viruses occurred more frequently since 2021 compared to pre-pandemic years, especially in younger children (2019 vs 2022, p < 0.01). CONCLUSION: Compared to pre-pandemic years, we observed a dramatic increase in pediatric RTIs with an incrementing spectrum of viruses and a predominance in Rhino/Enterovirus infections - leading to a high rate of hospital admissions, particularly in conjunction with other viruses. This caused an acute shortage in medical care and may also be followed by an increase of virus-triggered secondary chronic respiratory diseases like asthma-rendering a burden on the health system.

Antimicrobial Activity of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Cefiderocol, and Novel Darobactin Analogs against Multidrug-Resistant Pseudomonas aeruginosa Isolates from Pediatric and Adolescent Cystic Fibrosis Patients.

The emergence and spread of antimicrobial resistance (AMR) in Gram-negative pathogens, such as carbapenem-resistant Pseudomonas aeruginosa, pose an increasing threat to health care. Patients with immunodeficiencies or chronic pulmonary disease, like cystic fibrosis (CF), are particularly vulnerable to Pseudomonas infections and depend heavily on antibiotic therapy. To broaden limited treatment options, this study evaluated the potency of the recently licensed drugs ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), and cefiderocol (FDC) as well as two novel preclinical antibiotics, darobactins B (DAR B) and B9 (DAR B9), against clinical P. aeruginosa isolates derived from respiratory samples of CF patients. We observed high levels of resistance to all three newly licensed drugs, with cefiderocol exhibiting the best activity. From the 66 investigated P. aeruginosa isolates, a total of 53% were resistant to CZA, 49% to C/T, and 30% to FDC. Strikingly, 52 of the evaluated isolates were obtained from CF patients prior to market introduction of the drugs. Thus, our results suggest that resistance to CZA, C/T, and FDC may be due to preexisting resistance mechanisms. On the other hand, our two novel preclinical compounds performed better than (CZA and C/T) or close to (FDC) the licensed drugs-most likely due to the novel mode of action. Thus, our results highlight the necessity of global consistency in the area of antibiotic stewardship to prevent AMR from further impairing the potency of antibiotics in clinical practice. Ultimately, this study demonstrates the urgency to support the development of novel antimicrobials, preferably with a new mode of action such as darobactins B and B9, two very promising antimicrobial compounds for the treatment of critically ill patients suffering from multidrug-resistant Gram-negative (MRGN) infections. IMPORTANCE Antimicrobial resistance (AMR) represents an ever increasing threat to the health care system. Even recently licensed drugs are often not efficient for the treatment of infections caused by Gram-negative bacteria, like Pseudomonas aeruginosa, a causative agent of lung infections. To address this unmet medical need, innovative antibiotics, which possess a new mode of action, need to be developed. Here, the antibiogram of clinical isolates derived from cystic fibrosis patients was generated and new bicyclic heptapeptides, which inhibit the outer membrane protein BamA, exhibited strong activity, also against multidrug-resistant isolates.