Antibiotics

Variable outcomes have been reported with cefiderocol in infections due to carbapenem-resistant Acinetobacter baumannii (CRAB). Nonetheless, it may be the only option for metallo-beta-lactamase-producing strains. We describe an outbreak of NDM-CRAB infections treated with cefiderocol. Thirty-eight patients were colonized and/or infected. Thirteen patients developed a systemic infection. A clinical cure was achieved in 10 (83%) patients, one VAP and 9 BSIs, at day 7. In vitro, the activity of cefiderocol does not appear to match in vivo effectiveness using currently available commercial tests...

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of mortality, especially in healthcare environments. Reliable biomarkers that can accurately predict mortality in CDI patients are yet to be evaluated. Our study aims to evaluate the accuracy of several inflammatory biomarkers and hemogram-derived ratios in predicting mortality in CDI patients, such as the neutrophil-to-lymphocyte ratio (NLR), the systemic immune-inflammation index (SII), the platelet-to-neutrophil ratio (PNR), the derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP), the platelet-to-lymphocyte ratio (PLR), and procalcitonin (PCT)...

Antiviral peptides (AVPs) represent a promising strategy for addressing the global challenges of viral infections and their growing resistances to traditional drugs. Lab-based AVP discovery methods are resource-intensive, highlighting the need for efficient computational alternatives. In this study, we developed five non-trained but supervised multi-query similarity search models (MQSSMs) integrated into the StarPep toolbox. Rigorous testing and validation across diverse AVP datasets confirmed the models' robustness and reliability...

Multidrug-resistant (MDR) Staphylococcus aureus has been increasingly isolated from pigs and people in close contact with them, especially livestock-associated methicillin-resistant S. aureus (LA-MRSA). In this cross-sectional study, we investigated S. aureus colonization in pigs and farm workers, their resistance profile, and genetic background to estimate interspecies transmission potential within farms from Rio de Janeiro state, Brazil, between 2014 and 2019. We collected nasal swabs from 230 pigs and 27 workers from 16 and 10 farms, respectively...

Background : Typhoid fever caused by Salmonella enterica serovar Typhi (S. typhi) continues to pose a significant risk to public health in developing countries, including Pakistan. This study investigated the epidemiological factors linked to suspected and confirmed S. typhi infections in Peshawar's hospital population. Methodology : A total of 5735 blood samples of patients with suspected enteric fever were collected from September 2022 to November 2023. S. typhi infection was confirmed using microbiological culture of blood samples, biochemical-based tests, and DNA-sequencing methods...

Carbapenem-resistant Enterobacteriaceae infections are a considerable challenge for clinicians. In recent years, novel antibiotic options have resulted in a tremendous advance in medical therapy; however, current treatment options are primarily effective for resistance derived from serine-based carbapenemases. The Ambler class B metallo-β-lactamases (MBLs) remain a critical challenge with decidedly fewer effective options. One intriguing option for these MBL pathogens is the combination of ceftazidime-avibactam with aztreonam...

Open fractures and prosthetic joints are prone to bacterial infections, especially those involving biofilms, and are worsened by antibiotic inefficacy and resistance. This highlights the need for targeted treatments against orthopedic infections. LL-37, a human cathelicidin, is known for its antimicrobial properties. This study aimed to synthesize and evaluate LL-37-derived antimicrobial peptides (AMPs) for antibacterial efficacy and toxicity. Several truncated LL-37 analogues were created and tested against 18 bacterial strains, both ATCC and orthopedic clinical isolates, using MIC and MBC assays...

Antimicrobial resistance poses a major threat to global health as the number of efficient antimicrobials decreases and the number of resistant pathogens rises. Our research group has been actively involved in the design of novel antimicrobial drugs. The blueprints of these compounds were azolic heterocycles, particularly thiazole. Starting with oxadiazolines, our research group explored, one by one, the other five-membered heterocycles, developing more or less potent compounds. An overview of this research activity conducted by our research group allowed us to observe an evolution in the methodology used (from inhibition zone diameters to minimal inhibitory concentrations and antibiofilm potential determination) correlated with the design of azole compounds based on results obtained from molecular modeling...

Carbapenemase-producing Pseudomonas aeruginosa strains present a specific geographical distribution regarding the type of carbapenemase-encoding genes that they harbor. For more than twenty years, VIM-type enzymes were the only major carbapenemases that were detected among P. aeruginosa isolates in Greece until the emergence of NDM-1-encoding P. aeruginosa in early 2023. In the present study, we present the rapid reversal of the carbapenemase-producing P. aeruginosa epidemiology from bla VIM - to bla NDM -harbouring isolates that occurred in our hospital since then...

Infections due to Haemophilus influnezae require prompt treatment using beta-lactam antibiotics. We used a collection of 81 isolates obtained between 1940 and 2001 from several countries. Whole genome sequencing showed the high heterogeneity of these isolates but allowed us to track the acquisition of beta-lactamase, which was first detected in 1980. Modifications of the ftsI gene encoding the penicillin-binding protein 3, PBP3, also involved in resistance to beta-lactams, appeared in 1991. These modifications (G490E, A502V, R517H, and N526K) were associated with resistance to amoxicillin that was not relieved by a beta-lactamase inhibitor (clavulanic acid), but the isolates retained susceptibility to third-generation cephalosporins (3GC)...

BACKGROUND: Liposomal amphotericin B (L-AmB) has become the mainstay of treatment for severe invasive fungal infections. However, the potential for renal toxicity must be considered. AIMS: To evaluate the incidence of acute kidney injury (AKI) in critically ill patients receiving L-AmB for more than 48 h. METHODS: Retrospective, observational, single-center study. Clinical, demographic and laboratory variables were obtained automatically from the electronic medical record...

Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance ( mcr ) genes, notably mcr-1 , impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world...

Antimicrobial peptides (AMPs) are a promising class of therapeutic alternatives with broad-spectrum activity against resistant pathogens. Small AMPs like temporin-SHa ( 1 ) and its first-generation analog [G10a]-SHa ( 2 ) possess notable efficacy against Gram-positive and Gram-negative bacteria. In an effort to further improve this antimicrobial activity, second-generation analogs of 1 were synthesised by replacing the natural glycine residue at position-10 of the parent molecule with atypical amino acids, such as D-Phenylalanine, D-Tyrosine and (2-Naphthyl)-D-alanine, to study the effect of hydrophobicity on antimicrobial efficacy...

The current study was designed to assess the impact of L-carnitine (LC) supplementation in the drinking water of growing Alexandria-line rabbits on performance and physiological parameters. Two hundred eighty-eight 35-day-old rabbits were divided into four groups of twenty-four replicates each (seventy-two rabbits/treatment). The treatment groups were a control group without LC and three groups receiving 0.5, 1, and 1.5 g/L LC in the drinking water intermittently. The results showed that the group receiving 0...

To rapidly achieve ceftazidime target concentrations, a 2 g loading dose (LD) is recommended before continuous infusion, but its adequacy in critically ill patients, given their unique pharmacokinetics, needs investigation. This study included patients from six ICUs in Saint-Etienne and Paris, France, who received continuous ceftazidime infusion with plasma concentration measurements. Using MONOLIX and R, a pharmacokinetic (PK) model was developed, and the literature on ICU patient PK models was reviewed. Simulations calculated the LD needed to reach a 60 mg/L target concentration and assessed ceftazidime exposure for various regimens...

Aggressive pharmacokinetic (PK)/pharmacodynamic (PD) targets have shown better microbiological eradication rates and a lower propensity to develop resistant strains than conservative targets. We investigated whether meropenem blood levels, including aggressive PK/PD, were acceptable in terms of efficacy and safety using a meropenem regimen of 1 g infusion every 8 h over 3 h in patients undergoing continuous renal replacement therapy (CRRT) for septic acute kidney injury (AKI). Aggressive PK/PD targets were defined as the percentage of time that the free concentration (%fT) > 4 × minimal inhibitory concentration (MIC), the toxicity threshold was defined as a trough concentration >45 mg/L, and the percentage of achievement at each MIC was evaluated...

(1) Background: There is an ongoing discussion on the elution efficacy of antibiotic-impregnated cements. Our experiments were intended to clarify if there are differences in the antibiotic elution of HPLC compared with inhibition zone testing using eluates or PMMA discs. (2) Materials and Methods: Two cement brands with different concentrations of the active ingredient were tested in antimicrobial Kirby-Bauer (disc diffusion) assays. Cement platelets were directly applied on the agar plates and their zone of inhibition was measured...

The food chain acts as an entry point for antibiotic resistance to reach humans and environment. Because of the importance of the poultry sector, we investigated the prevalence and evolution of antibiotic resistance in Escherichia coli isolates from a series of 14,500 breeding hens and their farm environment during the rearing period. Samples included meconium from one-day-old breeders and fecal samples and boot swabs from the breeding sheds of pullets and adult hens. All E. coli isolates from one-day-old chicks, 77% from feces and 61% from boot swabs, were resistant to at least one antibiotic...

Upper gastrointestinal bleeding (UGIB) is a significant concern in children, contributing to 6-20% of cases in pediatric intensive care units. This study evaluates the roles of Helicobacter pylori ( H. pylori ) infection and non-steroidal anti-inflammatory drug (NSAID) usage in the etiology of UGIB in children, with a particular focus on trends observed during the COVID-19 pandemic. We conducted a retrospective analysis of 103 pediatric patients who underwent esophagogastroduodenoscopy (EGD) for UGIB between January 2015 and December 2023...

Bacteria are capable of remarkable adaptations to their environment, including undesirable bacterial resistance to antibacterial agents. One of the most serious cases is an infection caused by multidrug-resistant Staphylococcus aureus , which has unfortunately also spread outside hospitals. Therefore, the development of new effective antibacterial agents is extremely important to solve the increasing problem of bacterial resistance. The bacteriolytic enzyme autolysin E (AtlE) is a promising new drug target as it plays a key role in the degradation of peptidoglycan in the bacterial cell wall...