We evaluated the appropriateness of cefdinir prescribing in an integrated health care system. We performed a cross-sectional analysis of cefdinir prescribing for children aged 0 to 17 years old from 2005 to 2020 with acute otitis media, sinusitis, streptococcal pharyngitis, community-acquired pneumonia, urinary tract infection, and viral respiratory tract infections. The percentage of potentially inappropriate prescriptions was compared by location, provider specialty, and provider type using the chi-square test. A total of 93 748 cefdinir prescriptions were prescribed to pediatric patients, with 53 642 (57%) deemed as potentially inappropriate. Encounters in emergency and urgent care settings were more likely than ambulatory settings to be associated with inappropriate prescribing of cefdinir (P < .001). Non-pediatric-trained providers were responsible for 46.8% of the potentially inappropriate cefdinir prescriptions and were more likely to prescribe potentially inappropriate cefdinir prescriptions compared with pediatric-trained providers (P < .001). Advanced practice providers were more likely than physician providers to prescribe potentially inappropriate cefdinir prescriptions (P < .001).

Pseudomonas aeruginosa is a major cause of ventilator-associated pneumonia (VAP) and is increasingly associated with extensive antimicrobial resistance, limiting therapeutic options and contributing to poor clinical outcomes. The emergence of high-risk clones that combine multidrug resistance and virulence-associated traits represents a growing public health concern.In this study, 100 clinical P. aeruginosa isolates recovered from VAP patients were screened using culture-based identification and antimicrobial susceptibility testing. Two isolates exhibiting the most extensive resistance profiles, consistent with pandrug-resistant (PDR) phenotypes, and associated with fatal clinical outcomes were selected for whole-genome sequencing using Oxford Nanopore technology.Comprehensive genomic analyses were performed to characterize antimicrobial resistance determinants, chromosomal resistance mutations, virulence-associated genes, mobile genetic elements, genomic islands, and phylogenomic relationships. Both isolates were assigned to sequence type ST308 and serogroup O11, a globally disseminated high-risk lineage. Core-genome phylogenomic analysis of 52 genomes identified 144,617 informative SNPs across 5,085 shared core genes and showed that the two Egyptian isolates differed by only 74 core-genome SNPs while clustering within the international ST308 lineage.The isolates harbored an extensive resistome including blaNDM-1, blaOXA-10, blaOXA-488, qnrVC1, rmtF, sul1, sul2, floR, and msrE. High-confidence chromosomal resistance mutations were detected in gyrA (T83I), parC (S87L), oprD (Q402HfsTer99), nalC, nalD, and pmrB, supporting resistance to fluoroquinolones, carbapenems, and polymyxins. Two complete class 1 integrons and one In0 structure, all carrying the class 1 integrase IntI1, were identified, comprising integron-associated multidrug resistance modules containing qnrVC1, aadA11, aac(6')-II, dfrB5, sul1, qacEΔ1, rmtF, blaOXA-10, and blaPAC-1. In contrast, blaNDM-1 was located within a distinct ISVsa3-associated resistance island together with ble and msrE. Genomic island analysis further demonstrated the co-localization of key resistance determinants and the exoU virulence factor within predicted genomic islands.Both isolates carried a highly conserved virulome, including exoU, exoT, type VI secretion system components, iron-acquisition systems, and biofilm-associated genes. Collectively, these findings indicate the convergence of resistance islands, integron-associated multidrug resistance modules, chromosomal resistance mechanisms, and virulence-associated determinants within a globally disseminated ST308/O11 high-risk clone associated with fatal VAP cases in Egypt.To our knowledge, this study provides the first comprehensive genomic characterization of ST308/O11 P. aeruginosa exhibiting a pandrug-resistant phenotype based on the antimicrobial panel tested and associated with fatal ventilator-associated pneumonia in Egypt. Furthermore, by integrating cohort-level screening of 100 clinical isolates with comparative whole-genome analysis, this work provides additional insight into the genomic diversity of globally disseminated high-risk lineages through the accumulation of resistance and virulence determinants.

Procalcitonin (PCT)-guided therapy may optimize antibiotic use in respiratory infections and chronic lung diseases. This systematic review aimed to assess the role of PCT-guided protocols in reducing antibiotic duration, length of hospital and ICU stay, and clinical outcomes in patients with community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and chronic obstructive pulmonary disease (COPD). A secondary literature search was conducted using the databases PubMed and Google Scholar to identify the relevant studies published between January 2003 and December 2023. Eligible studies included peer-reviewed original research (clinical trials, observational, cohort, and case-control studies) evaluating PCT in CAP, VAP, HAP, or COPD, including viral and/or bacterial lower respiratory tract infections (LRTIs) in humans. The excluded studies were animal studies, studies not involving LRTIs, PCT studies lacking extractable data, and non-peer-reviewed editorials, opinions, and conference abstracts. Inconsistency across studies was assessed by heterogeneity analyses and publication bias using funnel plots. Twenty-four studies involving 16,134 patients were included. Across all conditions, PCT-guided therapy reduced antibiotic duration, particularly in CAP, without increasing mortality. Studies included in the CAP group reported that patients in the PCT group benefited from a shorter duration of therapy, with the treatment period decreasing from an average of 13.3±6.5 days in the control group to 11.7±6.2 days in the PCT group. Similarly, the PCT group had significantly reduced ICU stays. For COPD, hospital stay was significantly reduced, though fewer studies demonstrated ICU benefits. PCT-guided protocols may effectively help in better treatment strategies for CAP and COPD management.

SUMMARYMycoplasma pneumoniae pneumonia (MPP) is an acute respiratory infection caused by Mycoplasma pneumoniae (MP) and constitutes the primary cause of community-acquired pneumonia (CAP) among children aged 5 years and older in China. The clinical manifestations of MP-associated respiratory disease in children are diverse, ranging from mild upper respiratory symptoms to life-threatening pneumonia. Notably, during the implementation of nonpharmaceutical interventions (NPIs) aimed at curbing SARS-CoV-2 transmission, there was a significant decline in MP infection rates. However, a pronounced global resurgence of MP infections was documented in 2023-2024. The increasing global prevalence of macrolide resistance, particularly in China, coupled with limited alternative antibiotic options for children, increasing rates of coinfections, and the absence of a preventive vaccine, collectively exacerbate treatment challenges and increase the disease burden. Furthermore, the insufficient availability of MP nucleic acid testing and antimicrobial resistance surveillance in primary healthcare settings, coupled with the absence of a comprehensive epidemiological monitoring network, results in a vicious public health cycle. Recent advances and emerging genomic data have provided new insights into its pathogenesis and clinical management. Therefore, in this narrative review, we aim to (i) synthesize the current understanding of the etiological characteristics of MP and the present status of MPP diagnosis and treatment; (ii) analyze recent advances and drivers behind the global resurgence of MP infections; and (iii) propose integrated prevention and control strategies to increase the recognition of MPP and prevent unanticipated outbreaks.

After severe depletion of CD4 T cells in AIDS patients, they are not only prone to a first-time Nocardia infection, but also, even if cured, unable to form protective immune memory, leaving them susceptible to reinfection with the same pathogen. More seriously, in the absence of immune surveillance, irregular drug use can accelerate the selection of drug-resistant strains. A 32-year-old man with AIDS and persistent CD4+ count below 100 cells/μL for over three years (nadir 2 cells/μL) developed right lower lobe pneumonia caused by Nocardia farcinica four years before the current admission, which was cured with a TMP-SMX-containing regimen. The isolate was sensitive to trimethoprim-sulfamethoxazole (TMP-SMX), and the lesion nearly resolved after treatment. He was prescribed long-term TMP-SMX prophylaxis at discharge but stopped taking it on his own. One year before the current admission, he received sulfadiazine plus pyrimethamine for clinically diagnosed cerebral toxoplasmosis, but his adherence was poor and irregular. On current admission (day 1), he was readmitted with high fever and sepsis. Chest CT showed multiple cavities in the left lower lobe. Blood cultures flagged positive at 25 hours and were identified as Nocardia farcinica. The microbiologist reviewed his old records, found the previous nocardial history, and recommended bronchoalveolar lavage (BAL). BAL metagenomic next-generation sequencing again identified Nocardia farcinica, but susceptibility testing now showed resistance to TMP-SMX (MIC ≥8/152). He improved after switching to imipenem plus amikacin. He received intravenous imipenem plus amikacin for 14 days, followed by oral linezolid for 6 weeks. At the last follow-up (approximately one year after discharge), his CD4[+] had risen to only 11 cells/μL, and he had no further nocardial infection. This case shows that when CD4[+] stays below 100 for a long time, even a first nocardial infection can be cured but may leave insufficient immune memory, rendering the patient susceptible to subsequent infection. The distinction between true reinfection and late relapse could not be definitively established in the absence of strain-level homology data. Irregular, sub-therapeutic sulfonamide exposure, combined with a non-functional immune system, can select for resistant strains.