Journal of Antimicrobial Chemotherapy

OBJECTIVES: Cytomegalovirus (CMV) is the leading cause of congenital infection worldwide. Reference anti-CMV treatment is valganciclovir/ganciclovir, which is contraindicated in pregnancy given questions about teratogenicity. METHODS: We analysed reports from VigiBase, the world's largest safety database, and performed a disproportionality analysis of adverse pregnancy outcomes associated with (val)ganciclovir compared with any other drugs or with (val)aciclovir as comparators...

OBJECTIVES: Ceftazidime/avibactam and cefiderocol are two of the latest antibiotics with activity against a wide variety of Gram-negatives, including carbapenem-resistant Enterobacterales. We sought to describe the phenotypic and genotypic characteristics of ceftazidime/avibactam- and cefiderocol-resistant KPC-Klebsiella pneumoniae (KPC-Kp) detected during an outbreak in 2020 in the medical ICU of our hospital. METHODS: We collected 11 KPC-Kp isolates (6 clinical; 5 surveillance samples) resistant to ceftazidime/avibactam and cefiderocol from four ICU patients (November 2020 to January 2021), without prior exposure to these agents...

OBJECTIVES: We performed a systematic review and meta-analysis to estimate the effect of early active empirical antibiotics for MRSA on mortality, both in patients admitted with MRSA infections and in patients admitted with common infectious syndromes, for whom the causative pathogen may not have been MRSA. METHODS: A systematic literature search was conducted using Embase, MEDLINE, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from the earliest entry through to 26 April 2022...

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BACKGROUND: In 2019, a high-level quinolone-resistant Haemophilus haemolyticus strain (levofloxacin MIC = 16 mg/L) was isolated from a paediatric patient. In this study, we aimed to determine whether the quinolone resistance of H. haemolyticus could be transferred to Haemophilus influenzae and to identify the mechanism underlying the high-level quinolone resistance of H. haemolyticus. METHODS: A horizontal gene transfer assay to H. influenzae was performed using genomic DNA or PCR-amplified quinolone-targeting genes from the high-level quinolone-resistant H...

OBJECTIVES: To describe itraconazole and hydroxy-itraconazole pharmacokinetics following intravenous (IV) administration of a previously developed nanocrystal formulation (NCF) in haematopoietic cell transplant (HCT) recipients for prophylaxis of invasive fungal disease. METHODS: In a prospective Phase II study, 10 HCT recipients received itraconazole NCF administered in 2-hour infusions of 200 mg twice daily for 2 days, followed by 200 mg once daily until Day 14...

OBJECTIVES: Antibacterial antifolate drugs might have a wider role in the management of staphylococcal infection. One factor that could potentially limit their use in this context is pre-existing resistance. Here we explored the prevalence and genetic basis for resistance to these drugs in a large collection (n = 1470) of multidrug-resistant (MDR) Staphylococcus aureus. METHODS: Strains were subjected to susceptibility testing to detect resistance to trimethoprim, sulfamethoxazole, co-trimoxazole and the investigational drug, iclaprim...

Respiratory syncytial virus (RSV) is a leading cause of hospitalization and infant mortality worldwide. There are currently no approved vaccines against RSV, and immunoprophylaxis with the mAb palivizumab is limited to extremely vulnerable infants in resource-rich settings due to its high cost and the need for monthly injections throughout the RSV season. Nirsevimab (formerly MEDI8897) is a highly potent, long-acting, human, recombinant mAb that received approval for the prevention of RSV infection in newborns and infants during their first RSV season from the EMA and the UK's Medicines and Healthcare products Regulatory Agency in November 2022 based on positive results in Phase 2b and 3 clinical trials...

BACKGROUND: Aztreonam/avibactam is one of the last therapeutic options for treating infections caused by NDM-like-producing Enterobacterales. However, PBP3-modified and NDM-producing Escherichia coli strains that co-produce CMY-42 have been shown to be resistant to this drug combination. The aim of our study was to assess the in vitro activity of cefepime/taniborbactam and cefepime/zidebactam against such aztreonam/avibactam-resistant E. coli strains. METHODS: MIC values of aztreonam, aztreonam/avibactam, cefepime, cefepime/taniborbactam, cefepime/zidebactam and zidebactam alone were determined for 28 clinical aztreonam/avibactam-resistant E...

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No abstract text is available yet for this article.

OBJECTIVES: Limited evidence is available regarding alternative therapeutic agents to vancomycin in treating glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. This study assessed the effectiveness and safety of teicoplanin compared with vancomycin for treating GSEF bacteraemia. PATIENTS AND METHODS: This was a retrospective, non-inferiority cohort study. Patients aged ≥18 years who developed GSEF bacteraemia and received either teicoplanin or vancomycin were included...

OBJECTIVES: To describe and characterize the emergence of resistance to ceftolozane/tazobactam, ceftazidime/avibactam and imipenem/relebactam in a patient receiving ceftazidime/avibactam treatment for an MDR Pseudomonas aeruginosa CNS infection. METHODS: One baseline (PA1) and two post-exposure (PA2 and PA3) isolates obtained before and during treatment of a nosocomial P. aeruginosa meningoventriculitis were evaluated. MICs were determined by broth microdilution...

BACKGROUND: While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis. METHODS: E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with 'increased exposure susceptibility' to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0...

OBJECTIVES: Calcium-binding motifs are shared by multiple bacteriophage lysins; however, the influence of calcium on the enzymatic activity and host range of these enzymes is still not understood. To address this, ClyF, a chimeric lysin with a putative calcium-binding motif, was used as a model for in vitro and in vivo investigations. METHODS: The concentration of calcium bound to ClyF was determined by atomic absorption spectrometry. The influence of calcium on the structure, activity and host range of ClyF was assessed by circular dichroism and time-kill assays...

OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia...

The ongoing spread of antimicrobial resistance has made the treatment of uncomplicated urinary tract infections (UTIs) and urogenital gonorrhoea increasingly difficult. New oral treatment options are urgently needed. Gepotidacin (previously GSK2140944) is a novel, bactericidal, oral, 'first-in-class' triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by blocking two essential topoisomerase enzymes. Mutations in both enzymes would likely be necessary for resistance to occur, thus raising hopes that the drug will be able to maintain long-term effectiveness...

OBJECTIVES: To elucidate the role of a novel carbapenem-hydrolysing class D β-lactamase (RAD-1) from Riemerella anatipestifer. METHODS: We applied WGS and bioinformatic analysis to screen putative β-lactamase genes in R. anatipestifer SCVM0004. A putative class D β-lactamase gene was cloned into pET24a and transferred into Escherichia coli BL21 (DE3) for antibiotic susceptibility determination and protein purification. Meanwhile, the purified native protein was used to determine the enzymatic activities...

As one of a series of thematically linked reviews of the primary pharmacology of the β-lactam/β-lactamase inhibitor combination, ceftazidime/avibactam, this article reviews the microbiological findings in drug-exposed patients. Earlier articles in the series focused on basic in vitro and in vivo translational biology (J Antimicrob Chemother 2022; 77: 2321-40 and 2341-52) and the development and mechanisms of resistance in vitro (J Antimicrob Chemother 2023: Epub ahead of print. doi: 10.1093/jac/dkac449)...

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